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Biostatistics (also known as biometry) is a branch of
statistics Statistics (from German language, German: ', "description of a State (polity), state, a country") is the discipline that concerns the collection, organization, analysis, interpretation, and presentation of data. In applying statistics to a s ...
that applies statistical methods to a wide range of topics in
biology Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...
. It encompasses the design of biological
experiment An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs whe ...
s, the collection and analysis of data from those experiments and the interpretation of the results.


History


Biostatistics and genetics

Biostatistical modeling forms an important part of numerous modern biological theories.
Genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...
studies, since its beginning, used statistical concepts to understand observed experimental results. Some genetics scientists even contributed with statistical advances with the development of methods and tools.
Gregor Mendel Gregor Johann Mendel Order of Saint Augustine, OSA (; ; ; 20 July 1822 – 6 January 1884) was an Austrian Empire, Austrian biologist, meteorologist, mathematician, Augustinians, Augustinian friar and abbot of St Thomas's Abbey, Brno, St. Thom ...
started the genetics studies investigating genetics segregation patterns in families of peas and used statistics to explain the collected data. In the early 1900s, after the rediscovery of Mendel's Mendelian inheritance work, there were gaps in understanding between genetics and evolutionary Darwinism.
Francis Galton Sir Francis Galton (; 16 February 1822 – 17 January 1911) was an English polymath and the originator of eugenics during the Victorian era; his ideas later became the basis of behavioural genetics. Galton produced over 340 papers and b ...
tried to expand Mendel's discoveries with human data and proposed a different model with fractions of the heredity coming from each ancestral composing an infinite series. He called this the theory of " Law of Ancestral Heredity". His ideas were strongly disagreed by
William Bateson William Bateson (8 August 1861 – 8 February 1926) was an English biologist who was the first person to use the term genetics to describe the study of heredity, and the chief populariser of the ideas of Gregor Mendel following their rediscover ...
, who followed Mendel's conclusions, that genetic inheritance were exclusively from the parents, half from each of them. This led to a vigorous debate between the biometricians, who supported Galton's ideas, as
Raphael Weldon Walter Frank Raphael Weldon FRS (15 March 1860 – 13 April 1906), was an English evolutionary biologist and a founder of biometry. He was the joint founding editor of ''Biometrika'', with Francis Galton and Karl Pearson. Family Weldon was th ...
, Arthur Dukinfield Darbishire and
Karl Pearson Karl Pearson (; born Carl Pearson; 27 March 1857 – 27 April 1936) was an English biostatistician and mathematician. He has been credited with establishing the discipline of mathematical statistics. He founded the world's first university ...
, and Mendelians, who supported Bateson's (and Mendel's) ideas, such as
Charles Davenport Charles Benedict Davenport (June 1, 1866 – February 18, 1944) was a biologist and eugenicist influential in the American eugenics movement. Early life and education Davenport was born in Stamford, Connecticut on June 1, 1866, to Amzi Bened ...
and
Wilhelm Johannsen Wilhelm Johannsen (3 February 1857 – 11 November 1927) was a Danish pharmacist, botanist, plant physiologist, and geneticist. He is best known for coining the terms gene, phenotype and genotype, and for his 1903 "pure line" experiments in ...
. Later, biometricians could not reproduce Galton conclusions in different experiments, and Mendel's ideas prevailed. By the 1930s, models built on statistical reasoning had helped to resolve these differences and to produce the neo-Darwinian modern evolutionary synthesis. Solving these differences also allowed to define the concept of population genetics and brought together genetics and evolution. The three leading figures in the establishment of
population genetics Population genetics is a subfield of genetics that deals with genetic differences within and among populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as Adaptation (biology), adaptation, s ...
and this synthesis all relied on statistics and developed its use in biology. *
Ronald Fisher Sir Ronald Aylmer Fisher (17 February 1890 – 29 July 1962) was a British polymath who was active as a mathematician, statistician, biologist, geneticist, and academic. For his work in statistics, he has been described as "a genius who a ...
worked alongside statistician Betty Allan developing several basic statistical methods in support of his work studying the crop experiments at
Rothamsted Research Rothamsted Research, previously known as the Rothamsted Experimental Station and then the Institute of Arable Crops Research, is one of the oldest agricultural experiment station, agricultural research institutions in the world, having been founde ...
, published in Fisher's books
Statistical Methods for Research Workers ''Statistical Methods for Research Workers'' is a classic book on statistics, written by the statistician R. A. Fisher. It is considered by some to be one of the 20th century's most influential books on statistical methods, together with his '' T ...
(1925) and
The Genetical Theory of Natural Selection ''The Genetical Theory of Natural Selection'' is a book by Ronald Fisher which combines Mendelian inheritance, Mendelian genetics with Charles Darwin's theory of natural selection, with Fisher being the first to argue that "Mendelism therefore va ...
(1930), as well as Allan's scientific papers. Fisher went on to give many contributions to genetics and statistics. Some of them include the
ANOVA Analysis of variance (ANOVA) is a family of statistical methods used to compare the means of two or more groups by analyzing variance. Specifically, ANOVA compares the amount of variation ''between'' the group means to the amount of variation ''w ...
,
p-value In null-hypothesis significance testing, the ''p''-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis is correct. A very small ''p''-value means ...
concepts,
Fisher's exact test Fisher's exact test (also Fisher-Irwin test) is a statistical significance test used in the analysis of contingency tables. Although in practice it is employed when sample sizes are small, it is valid for all sample sizes. The test assumes that a ...
and Fisher's equation for
population dynamics Population dynamics is the type of mathematics used to model and study the size and age composition of populations as dynamical systems. Population dynamics is a branch of mathematical biology, and uses mathematical techniques such as differenti ...
. He is credited for the sentence "Natural selection is a mechanism for generating an exceedingly high degree of improbability". * Sewall G. Wright developed ''F''-statistics and methods of computing them and defined
inbreeding coefficient The coefficient of relationship is a measure of the degree of consanguinity (or biological relationship) between two individuals. The term coefficient of relationship was defined by Sewall Wright in 1922, and was derived from his definition of ...
. * J. B. S. Haldane's book, ''The Causes of Evolution'', reestablished natural selection as the premier mechanism of evolution by explaining it in terms of the mathematical consequences of Mendelian genetics. He also developed the theory of
primordial soup Primordial soup, also known as prebiotic soup and Haldane soup, is the hypothetical set of conditions present on the Earth around 3.7 to 4.0 billion years ago. It is an aspect of the heterotrophic theory (also known as the Oparin–Haldane hypothes ...
. These and other biostatisticians, mathematical biologists, and statistically inclined geneticists helped bring together
evolutionary biology Evolutionary biology is the subfield of biology that studies the evolutionary processes such as natural selection, common descent, and speciation that produced the diversity of life on Earth. In the 1930s, the discipline of evolutionary biolo ...
and
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...
into a consistent, coherent whole that could begin to be
quantitative Quantitative may refer to: * Quantitative research, scientific investigation of quantitative properties * Quantitative analysis (disambiguation) * Quantitative verse, a metrical system in poetry * Statistics, also known as quantitative analysis ...
ly modeled. In parallel to this overall development, the pioneering work of
D'Arcy Thompson Sir D'Arcy Wentworth Thompson CB FRS FRSE (2 May 1860 – 21 June 1948) was a Scottish biologist, mathematician and classics scholar. He was a pioneer of mathematical and theoretical biology, travelled on expeditions to the Bering Strait ...
in ''On Growth and Form'' also helped to add quantitative discipline to biological study. Despite the fundamental importance and frequent necessity of statistical reasoning, there may nonetheless have been a tendency among biologists to distrust or deprecate results which are not qualitatively apparent. One anecdote describes
Thomas Hunt Morgan Thomas Hunt Morgan (September 25, 1866 – December 4, 1945) was an Americans, American evolutionary biologist, geneticist, Embryology, embryologist, and science author who won the Nobel Prize in Physiology or Medicine in 1933 for discoveries e ...
banning the Friden calculator from his department at
Caltech The California Institute of Technology (branded as Caltech) is a private university, private research university in Pasadena, California, United States. The university is responsible for many modern scientific advancements and is among a small g ...
, saying "Well, I am like a guy who is prospecting for gold along the banks of the Sacramento River in 1849. With a little intelligence, I can reach down and pick up big nuggets of gold. And as long as I can do that, I'm not going to let any people in my department waste scarce resources in
placer mining Placer mining () is the mining of stream bed deposits for minerals. This may be done by open-pit mining or by various surface excavating equipment or tunneling equipment. Placer mining is frequently used for precious metal deposits (particularly ...
."


Research planning

Any research in
life sciences This list of life sciences comprises the branches of science that involve the scientific study of life – such as microorganisms, plants, and animals including human beings. This science is one of the two major branches of natural science, ...
is proposed to answer a scientific question we might have. To answer this question with a high certainty, we need
accurate Accuracy and precision are two measures of ''observational error''. ''Accuracy'' is how close a given set of measurements (observations or readings) are to their ''true value''. ''Precision'' is how close the measurements are to each other. The ...
results. The correct definition of the main
hypothesis A hypothesis (: hypotheses) is a proposed explanation for a phenomenon. A scientific hypothesis must be based on observations and make a testable and reproducible prediction about reality, in a process beginning with an educated guess o ...
and the research plan will reduce errors while taking a decision in understanding a phenomenon. The research plan might include the research question, the hypothesis to be tested, the
experimental design The design of experiments (DOE), also known as experiment design or experimental design, is the design of any task that aims to describe and explain the variation of information under conditions that are hypothesized to reflect the variation. ...
,
data collection Data collection or data gathering is the process of gathering and measuring information on targeted variables in an established system, which then enables one to answer relevant questions and evaluate outcomes. Data collection is a research com ...
methods,
data analysis Data analysis is the process of inspecting, Data cleansing, cleansing, Data transformation, transforming, and Data modeling, modeling data with the goal of discovering useful information, informing conclusions, and supporting decision-making. Da ...
perspectives and costs involved. It is essential to carry the study based on the three basic principles of experimental statistics:
randomization Randomization is a statistical process in which a random mechanism is employed to select a sample from a population or assign subjects to different groups.Oxford English Dictionary "randomization" The process is crucial in ensuring the random alloc ...
, replication, and local control.


Research question

The research question will define the objective of a study. The research will be headed by the question, so it needs to be concise, at the same time it is focused on interesting and novel topics that may improve science and knowledge and that field. To define the way to ask the scientific question, an exhaustive
literature review A literature review is an overview of previously published works on a particular topic. The term can refer to a full scholarly paper or a section of a scholarly work such as books or articles. Either way, a literature review provides the rese ...
might be necessary. So the research can be useful to add value to the
scientific community The scientific community is a diverse network of interacting scientists. It includes many "working group, sub-communities" working on particular scientific fields, and within particular institutions; interdisciplinary and cross-institutional acti ...
.


Hypothesis definition

Once the aim of the study is defined, the possible answers to the research question can be proposed, transforming this question into a
hypothesis A hypothesis (: hypotheses) is a proposed explanation for a phenomenon. A scientific hypothesis must be based on observations and make a testable and reproducible prediction about reality, in a process beginning with an educated guess o ...
. The main propose is called
null hypothesis The null hypothesis (often denoted ''H''0) is the claim in scientific research that the effect being studied does not exist. The null hypothesis can also be described as the hypothesis in which no relationship exists between two sets of data o ...
(H0) and is usually based on a permanent knowledge about the topic or an obvious occurrence of the phenomena, sustained by a deep literature review. We can say it is the standard expected answer for the data under the situation in
test Test(s), testing, or TEST may refer to: * Test (assessment), an educational assessment intended to measure the respondents' knowledge or other abilities Arts and entertainment * ''Test'' (2013 film), an American film * ''Test'' (2014 film) ...
. In general, HO assumes no association between treatments. On the other hand, the
alternative hypothesis In statistical hypothesis testing, the alternative hypothesis is one of the proposed propositions in the hypothesis test. In general the goal of hypothesis test is to demonstrate that in the given condition, there is sufficient evidence supporting ...
is the denial of HO. It assumes some degree of association between the treatment and the outcome. Although, the hypothesis is sustained by question research and its expected and unexpected answers. As an example, consider groups of similar animals (mice, for example) under two different diet systems. The research question would be: what is the best diet? In this case, H0 would be that there is no difference between the two diets in mice
metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
(H0: μ1 = μ2) and the
alternative hypothesis In statistical hypothesis testing, the alternative hypothesis is one of the proposed propositions in the hypothesis test. In general the goal of hypothesis test is to demonstrate that in the given condition, there is sufficient evidence supporting ...
would be that the diets have different effects over animals metabolism (H1: μ1 ≠ μ2). The
hypothesis A hypothesis (: hypotheses) is a proposed explanation for a phenomenon. A scientific hypothesis must be based on observations and make a testable and reproducible prediction about reality, in a process beginning with an educated guess o ...
is defined by the researcher, according to his/her interests in answering the main question. Besides that, the
alternative hypothesis In statistical hypothesis testing, the alternative hypothesis is one of the proposed propositions in the hypothesis test. In general the goal of hypothesis test is to demonstrate that in the given condition, there is sufficient evidence supporting ...
can be more than one hypothesis. It can assume not only differences across observed parameters, but their degree of differences (''i.e.'' higher or shorter).


Sampling

Usually, a study aims to understand an effect of a phenomenon over a
population Population is a set of humans or other organisms in a given region or area. Governments conduct a census to quantify the resident population size within a given jurisdiction. The term is also applied to non-human animals, microorganisms, and pl ...
. In
biology Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, History of life, origin, evolution, and ...
, a
population Population is a set of humans or other organisms in a given region or area. Governments conduct a census to quantify the resident population size within a given jurisdiction. The term is also applied to non-human animals, microorganisms, and pl ...
is defined as all the
individual An individual is one that exists as a distinct entity. Individuality (or self-hood) is the state or quality of living as an individual; particularly (in the case of humans) as a person unique from other people and possessing one's own needs or g ...
s of a given
species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...
, in a specific area at a given time. In biostatistics, this concept is extended to a variety of collections possible of study. Although, in biostatistics, a
population Population is a set of humans or other organisms in a given region or area. Governments conduct a census to quantify the resident population size within a given jurisdiction. The term is also applied to non-human animals, microorganisms, and pl ...
is not only the individuals, but the total of one specific component of their
organism An organism is any life, living thing that functions as an individual. Such a definition raises more problems than it solves, not least because the concept of an individual is also difficult. Many criteria, few of them widely accepted, have be ...
s, as the whole
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
, or all the sperm
cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...
, for animals, or the total leaf area, for a plant, for example. It is not possible to take the measures from all the elements of a
population Population is a set of humans or other organisms in a given region or area. Governments conduct a census to quantify the resident population size within a given jurisdiction. The term is also applied to non-human animals, microorganisms, and pl ...
. Because of that, the sampling process is very important for
statistical inference Statistical inference is the process of using data analysis to infer properties of an underlying probability distribution.Upton, G., Cook, I. (2008) ''Oxford Dictionary of Statistics'', OUP. . Inferential statistical analysis infers properties of ...
. Sampling is defined as to randomly get a representative part of the entire population, to make posterior inferences about the population. So, the sample might catch the most variability across a population. The
sample size Sample size determination or estimation is the act of choosing the number of observations or replicates to include in a statistical sample. The sample size is an important feature of any empirical study in which the goal is to make inferences abo ...
is determined by several things, since the scope of the research to the resources available. In
clinical research Clinical research is a branch of medical research that involves people and aims to determine the effectiveness (efficacy) and safety of medications, devices, diagnostic products, and treatment regimens intended for improving human health. The ...
, the trial type, as inferiority, equivalence, and
superior Superior may refer to: *Superior (hierarchy), something which is higher in a hierarchical structure of any kind Places * Superior (proposed U.S. state), an unsuccessful proposal for the Upper Peninsula of Michigan to form a separate state *Lak ...
ity is a key in determining sample
size Size in general is the Magnitude (mathematics), magnitude or dimensions of a thing. More specifically, ''geometrical size'' (or ''spatial size'') can refer to three geometrical measures: length, area, or volume. Length can be generalized ...
.


Experimental design

Experimental designs sustain those basic principles of experimental statistics. There are three basic experimental designs to randomly allocate treatments in all plots of the
experiment An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs whe ...
. They are
completely randomized design In the design of experiments, completely randomized designs are for studying the effects of one primary factor without the need to take other nuisance variables into account. This article describes completely randomized designs that have one primary ...
,
randomized block design In the statistical theory of the design of experiments, blocking is the arranging of experimental units that are similar to one another in groups (blocks) based on one or more variables. These variables are chosen carefully to minimize the effect ...
, and factorial designs. Treatments can be arranged in many ways inside the experiment. In
agriculture Agriculture encompasses crop and livestock production, aquaculture, and forestry for food and non-food products. Agriculture was a key factor in the rise of sedentary human civilization, whereby farming of domesticated species created ...
, the correct
experimental design The design of experiments (DOE), also known as experiment design or experimental design, is the design of any task that aims to describe and explain the variation of information under conditions that are hypothesized to reflect the variation. ...
is the root of a good study and the arrangement of treatments within the study is essential because environment largely affects the plots (
plants Plants are the eukaryotes that form the kingdom Plantae; they are predominantly photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with cyanobacteria to produce sugars f ...
,
livestock Livestock are the Domestication, domesticated animals that are raised in an Agriculture, agricultural setting to provide labour and produce diversified products for consumption such as meat, Egg as food, eggs, milk, fur, leather, and wool. The t ...
,
microorganism A microorganism, or microbe, is an organism of microscopic scale, microscopic size, which may exist in its unicellular organism, single-celled form or as a Colony (biology)#Microbial colonies, colony of cells. The possible existence of unseen ...
s). These main arrangements can be found in the literature under the names of " lattices", "incomplete blocks", " split plot", "augmented blocks", and many others. All of the designs might include control plots, determined by the researcher, to provide an error estimation during
inference Inferences are steps in logical reasoning, moving from premises to logical consequences; etymologically, the word '' infer'' means to "carry forward". Inference is theoretically traditionally divided into deduction and induction, a distinct ...
. In
clinical studies Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
, the samples are usually smaller than in other biological studies, and in most cases, the environment effect can be controlled or measured. It is common to use randomized controlled clinical trials, where results are usually compared with
observational study In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample (statistics), sample to a statistical population, population where the dependent and independent variables, independ ...
designs such as case–control or
cohort Cohort or cohortes may refer to: Cohort Sociological * Cohort (military unit), the basic tactical unit of a Roman legion * Cohort (educational group), a group of students working together through the same academic curriculum Scientific * Cohort ...
.


Data collection

Data collection methods must be considered in research planning, because it highly influences the sample size and experimental design. Data collection varies according to the type of data. For
qualitative data Qualitative properties are properties that are observed and can generally not be measured with a numerical result, unlike Quantitative property, quantitative properties, which have numerical characteristics. Description Qualitative properties a ...
, collection can be done with structured questionnaires or by observation, considering presence or intensity of disease, using score criterion to categorize levels of occurrence. For
quantitative data Quantitative research is a research strategy that focuses on quantifying the collection and analysis of data. It is formed from a deductive approach where emphasis is placed on the testing of theory, shaped by empiricist and positivist philoso ...
, collection is done by measuring numerical information using instruments. In agriculture and biology studies, yield data and its components can be obtained by metric measures. However, pest and disease injuries in plants are obtained by observation, considering score scales for levels of damage. Especially, in genetic studies, modern methods for data collection in field and laboratory should be considered, as high-throughput platforms for phenotyping and genotyping. These tools allow bigger experiments, while turn possible evaluate many plots in lower time than a human-based only method for data collection. Finally, all data collected of interest must be stored in an organized data frame for further analysis.


Analysis and data interpretation


Descriptive tools

Data can be represented through tables or
graphical Graphics () are visual images or designs on some surface, such as a wall, canvas, screen, paper, or stone, to inform, illustrate, or entertain. In contemporary usage, it includes a pictorial representation of the data, as in design and manufactu ...
representation, such as line charts, bar charts, histograms, scatter plot. Also, measures of central tendency and variability can be very useful to describe an overview of the data. Follow some examples:


Frequency tables

One type of table is the
frequency Frequency is the number of occurrences of a repeating event per unit of time. Frequency is an important parameter used in science and engineering to specify the rate of oscillatory and vibratory phenomena, such as mechanical vibrations, audio ...
table, which consists of data arranged in rows and columns, where the frequency is the number of occurrences or repetitions of data. Frequency can be: Absolute: represents the number of times that a determined value appear; N = f_1 + f_2 + f_3 + ... + f_n Relative: obtained by the division of the absolute frequency by the total number; n_i = \frac In the next example, we have the number of genes in ten
operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...
s of the same organism. :


Line graph

Line graph In the mathematics, mathematical discipline of graph theory, the line graph of an undirected graph is another graph that represents the adjacencies between edge (graph theory), edges of . is constructed in the following way: for each edge i ...
s represent the variation of a value over another metric, such as time. In general, values are represented in the vertical axis, while the time variation is represented in the horizontal axis.


Bar chart

A
bar chart A bar chart or bar graph is a chart or graph that presents categorical variable, categorical data with rectangular bars with heights or lengths proportional to the values that they represent. The bars can be plotted vertically or horizontally. A ...
is a graph that shows categorical data as bars presenting heights (vertical bar) or widths (horizontal bar) proportional to represent values. Bar charts provide an image that could also be represented in a tabular format. In the bar chart example, we have the birth rate in Brazil for the December months from 2010 to 2016. The sharp fall in December 2016 reflects the outbreak of
Zika virus Zika virus (ZIKV; pronounced or ) is a member of the virus family ''Flaviviridae''. It is spread by daytime-active ''Aedes'' mosquitoes, such as '' A. aegypti'' and '' A. albopictus''. Its name comes from the Ziika Forest of Uganda, where ...
in the birth rate in Brazil.


Histograms

The
histogram A histogram is a visual representation of the frequency distribution, distribution of quantitative data. To construct a histogram, the first step is to Data binning, "bin" (or "bucket") the range of values— divide the entire range of values in ...
(or frequency distribution) is a graphical representation of a dataset tabulated and divided into uniform or non-uniform classes. It was first introduced by
Karl Pearson Karl Pearson (; born Carl Pearson; 27 March 1857 – 27 April 1936) was an English biostatistician and mathematician. He has been credited with establishing the discipline of mathematical statistics. He founded the world's first university ...
.


Scatter plot

A
scatter plot A scatter plot, also called a scatterplot, scatter graph, scatter chart, scattergram, or scatter diagram, is a type of plot or mathematical diagram using Cartesian coordinates to display values for typically two variables for a set of dat ...
is a mathematical diagram that uses Cartesian coordinates to display values of a dataset. A scatter plot shows the data as a set of points, each one presenting the value of one variable determining the position on the horizontal axis and another variable on the vertical axis. They are also called scatter graph, scatter chart, scattergram, or scatter diagram.


Mean

The
arithmetic mean In mathematics and statistics, the arithmetic mean ( ), arithmetic average, or just the ''mean'' or ''average'' is the sum of a collection of numbers divided by the count of numbers in the collection. The collection is often a set of results fr ...
is the sum of a collection of values () divided by the number of items of this collection (). : \bar = \frac\left (\sum_^n\right ) = \frac


Median

The
median The median of a set of numbers is the value separating the higher half from the lower half of a Sample (statistics), data sample, a statistical population, population, or a probability distribution. For a data set, it may be thought of as the “ ...
is the value in the middle of a dataset.


Mode

The
mode Mode ( meaning "manner, tune, measure, due measure, rhythm, melody") may refer to: Arts and entertainment * MO''D''E (magazine), a defunct U.S. women's fashion magazine * ''Mode'' magazine, a fictional fashion magazine which is the setting fo ...
is the value of a set of data that appears most often.


Box plot

Box plot In descriptive statistics, a box plot or boxplot is a method for demonstrating graphically the locality, spread and skewness groups of numerical data through their quartiles. In addition to the box on a box plot, there can be lines (which are ca ...
is a method for graphically depicting groups of numerical data. The maximum and minimum values are represented by the lines, and the interquartile range (IQR) represent 25–75% of the data.
Outlier In statistics, an outlier is a data point that differs significantly from other observations. An outlier may be due to a variability in the measurement, an indication of novel data, or it may be the result of experimental error; the latter are ...
s may be plotted as circles.


Correlation coefficients

Although correlations between two different kinds of data could be inferred by graphs, such as scatter plot, it is necessary validate this though numerical information. For this reason,
correlation coefficient A correlation coefficient is a numerical measure of some type of linear correlation, meaning a statistical relationship between two variables. The variables may be two columns of a given data set of observations, often called a sample, or two c ...
s are required. They provide a numerical value that reflects the strength of an association.


Pearson correlation coefficient

Pearson correlation coefficient In statistics, the Pearson correlation coefficient (PCC) is a correlation coefficient that measures linear correlation between two sets of data. It is the ratio between the covariance of two variables and the product of their standard deviatio ...
is a measure of association between two variables, X and Y. This coefficient, usually represented by ''ρ'' (rho) for the population and ''r'' for the sample, assumes values between −1 and 1, where ''ρ'' = 1 represents a perfect positive correlation, ''ρ'' = −1 represents a perfect negative correlation, and ''ρ'' = 0 is no linear correlation.


Inferential statistics

It is used to make
inference Inferences are steps in logical reasoning, moving from premises to logical consequences; etymologically, the word '' infer'' means to "carry forward". Inference is theoretically traditionally divided into deduction and induction, a distinct ...
s about an unknown population, by estimation and/or hypothesis testing. In other words, it is desirable to obtain parameters to describe the population of interest, but since the data is limited, it is necessary to make use of a representative sample in order to estimate them. With that, it is possible to test previously defined hypotheses and apply the conclusions to the entire population. The
standard error of the mean The standard error (SE) of a statistic (usually an estimator of a parameter, like the average or mean) is the standard deviation of its sampling distribution or an estimate of that standard deviation. In other words, it is the standard deviatio ...
is a measure of variability that is crucial to do inferences. *
Hypothesis testing A statistical hypothesis test is a method of statistical inference used to decide whether the data provide sufficient evidence to reject a particular hypothesis. A statistical hypothesis test typically involves a calculation of a test statistic. T ...
Hypothesis testing is essential to make inferences about populations aiming to answer research questions, as settled in "Research planning" section. Authors defined four steps to be set: # ''The hypothesis to be tested'': as stated earlier, we have to work with the definition of a
null hypothesis The null hypothesis (often denoted ''H''0) is the claim in scientific research that the effect being studied does not exist. The null hypothesis can also be described as the hypothesis in which no relationship exists between two sets of data o ...
(H0), that is going to be tested, and an
alternative hypothesis In statistical hypothesis testing, the alternative hypothesis is one of the proposed propositions in the hypothesis test. In general the goal of hypothesis test is to demonstrate that in the given condition, there is sufficient evidence supporting ...
. But they must be defined before the experiment implementation. # ''Significance level and decision rule'': A decision rule depends on the
level of significance Type I error, or a false positive, is the erroneous rejection of a true null hypothesis in statistical hypothesis testing. A type II error, or a false negative, is the erroneous failure in bringing about appropriate rejection of a false null hyp ...
, or in other words, the acceptable error rate (α). It is easier to think that we define a ''critical value'' that determines the statistical significance when a
test statistic Test statistic is a quantity derived from the sample for statistical hypothesis testing.Berger, R. L.; Casella, G. (2001). ''Statistical Inference'', Duxbury Press, Second Edition (p.374) A hypothesis test is typically specified in terms of a tes ...
is compared with it. So, α also has to be predefined before the experiment. # ''Experiment and statistical analysis'': This is when the experiment is really implemented following the appropriate
experimental design The design of experiments (DOE), also known as experiment design or experimental design, is the design of any task that aims to describe and explain the variation of information under conditions that are hypothesized to reflect the variation. ...
, data is collected and the more suitable statistical tests are evaluated. # ''Inference'': Is made when the
null hypothesis The null hypothesis (often denoted ''H''0) is the claim in scientific research that the effect being studied does not exist. The null hypothesis can also be described as the hypothesis in which no relationship exists between two sets of data o ...
is rejected or not rejected, based on the evidence that the comparison of
p-value In null-hypothesis significance testing, the ''p''-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis is correct. A very small ''p''-value means ...
s and α brings. It is pointed that the failure to reject H0 just means that there is not enough evidence to support its rejection, but not that this hypothesis is true. * Confidence intervals A confidence interval is a range of values that can contain the true real parameter value in given a certain level of confidence. The first step is to estimate the best-unbiased estimate of the population parameter. The upper value of the interval is obtained by the sum of this estimate with the multiplication between the standard error of the mean and the confidence level. The calculation of lower value is similar, but instead of a sum, a subtraction must be applied.


Statistical considerations


Power and statistical error

When testing a hypothesis, there are two types of statistic errors possible:
Type I error Type I error, or a false positive, is the erroneous rejection of a true null hypothesis in statistical hypothesis testing. A type II error, or a false negative, is the erroneous failure in bringing about appropriate rejection of a false null hy ...
and
Type II error Type I error, or a false positive, is the erroneous rejection of a true null hypothesis in statistical hypothesis testing. A type II error, or a false negative, is the erroneous failure in bringing about appropriate rejection of a false null hy ...
. * The type I error or
false positive A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resu ...
is the incorrect rejection of a true null hypothesis * The type II error or
false negative A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resu ...
is the failure to reject a false
null hypothesis The null hypothesis (often denoted ''H''0) is the claim in scientific research that the effect being studied does not exist. The null hypothesis can also be described as the hypothesis in which no relationship exists between two sets of data o ...
. The
significance level In statistical hypothesis testing, a result has statistical significance when a result at least as "extreme" would be very infrequent if the null hypothesis were true. More precisely, a study's defined significance level, denoted by \alpha, is the ...
denoted by α is the type I error rate and should be chosen before performing the test. The type II error rate is denoted by β and statistical power of the test is 1 − β.


p-value

The
p-value In null-hypothesis significance testing, the ''p''-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis is correct. A very small ''p''-value means ...
is the probability of obtaining results as extreme as or more extreme than those observed, assuming the
null hypothesis The null hypothesis (often denoted ''H''0) is the claim in scientific research that the effect being studied does not exist. The null hypothesis can also be described as the hypothesis in which no relationship exists between two sets of data o ...
(H0) is true. It is also called the calculated probability. It is common to confuse the p-value with the significance level (α), but, the α is a predefined threshold for calling significant results. If p is less than α, the null hypothesis (H0) is rejected.


Multiple testing

In multiple tests of the same hypothesis, the probability of the occurrence of
false positives A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test res ...
(familywise error rate) increase and a strategy is needed to account for this occurrence. This is commonly achieved by using a more stringent threshold to reject null hypotheses. The
Bonferroni correction In statistics, the Bonferroni correction is a method to counteract the multiple comparisons problem. Background The method is named for its use of the Bonferroni inequalities. Application of the method to confidence intervals was described by ...
defines an acceptable global significance level, denoted by α* and each test is individually compared with a value of α = α*/m. This ensures that the familywise error rate in all m tests, is less than or equal to α*. When m is large, the Bonferroni correction may be overly conservative. An alternative to the Bonferroni correction is to control the false discovery rate (FDR). The FDR controls the expected proportion of the rejected null hypotheses (the so-called discoveries) that are false (incorrect rejections). This procedure ensures that, for independent tests, the false discovery rate is at most q*. Thus, the FDR is less conservative than the Bonferroni correction and have more power, at the cost of more false positives.


Mis-specification and robustness checks

The main hypothesis being tested (e.g., no association between treatments and outcomes) is often accompanied by other technical assumptions (e.g., about the form of the probability distribution of the outcomes) that are also part of the null hypothesis. When the technical assumptions are violated in practice, then the null may be frequently rejected even if the main hypothesis is true. Such rejections are said to be due to model mis-specification. Verifying whether the outcome of a statistical test does not change when the technical assumptions are slightly altered (so-called robustness checks) is the main way of combating mis-specification.


Model selection criteria

Model criteria selection will select or model that more approximate true model. The Akaike's Information Criterion (AIC) and The Bayesian Information Criterion (BIC) are examples of asymptotically efficient criteria.


Developments and big data

Recent developments have made a large impact on biostatistics. Two important changes have been the ability to collect data on a high-throughput scale, and the ability to perform much more complex analysis using computational techniques. This comes from the development in areas as
sequencing In genetics and biochemistry, sequencing means to determine the primary structure (sometimes incorrectly called the primary sequence) of an unbranched biopolymer. Sequencing results in a symbolic linear depiction known as a sequence which succ ...
technologies,
Bioinformatics Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...
and
Machine learning Machine learning (ML) is a field of study in artificial intelligence concerned with the development and study of Computational statistics, statistical algorithms that can learn from data and generalise to unseen data, and thus perform Task ( ...
(
Machine learning in bioinformatics Machine learning in bioinformatics is the application of machine learning algorithms to bioinformatics, including genomics, proteomics, microarrays, systems biology, evolution, and text mining. Prior to the emergence of machine learning, bioinfor ...
).


Use in high-throughput data

New biomedical technologies like
microarrays A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a solid substrate—usually a glass slide or silicon thin-film cell� ...
, next-generation sequencers (for genomics) and
mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...
(for proteomics) generate enormous amounts of data, allowing many tests to be performed simultaneously. Careful analysis with biostatistical methods is required to separate the signal from the noise. For example, a microarray could be used to measure many thousands of genes simultaneously, determining which of them have different expression in diseased cells compared to normal cells. However, only a fraction of genes will be differentially expressed.
Multicollinearity In statistics, multicollinearity or collinearity is a situation where the predictors in a regression model are linearly dependent. Perfect multicollinearity refers to a situation where the predictive variables have an ''exact'' linear rela ...
often occurs in high-throughput biostatistical settings. Due to high intercorrelation between the predictors (such as
gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...
levels), the information of one predictor might be contained in another one. It could be that only 5% of the predictors are responsible for 90% of the variability of the response. In such a case, one could apply the biostatistical technique of dimension reduction (for example via principal component analysis). Classical statistical techniques like linear or
logistic regression In statistics, a logistic model (or logit model) is a statistical model that models the logit, log-odds of an event as a linear function (calculus), linear combination of one or more independent variables. In regression analysis, logistic regres ...
and
linear discriminant analysis Linear discriminant analysis (LDA), normal discriminant analysis (NDA), canonical variates analysis (CVA), or discriminant function analysis is a generalization of Fisher's linear discriminant, a method used in statistics and other fields, to fi ...
do not work well for high dimensional data (i.e. when the number of observations n is smaller than the number of features or predictors p: n < p). As a matter of fact, one can get quite high R2-values despite very low predictive power of the statistical model. These classical statistical techniques (esp.
least squares The method of least squares is a mathematical optimization technique that aims to determine the best fit function by minimizing the sum of the squares of the differences between the observed values and the predicted values of the model. The me ...
linear regression) were developed for low dimensional data (i.e. where the number of observations n is much larger than the number of predictors p: n >> p). In cases of high dimensionality, one should always consider an independent validation test set and the corresponding residual sum of squares (RSS) and R2 of the validation test set, not those of the training set. Often, it is useful to pool information from multiple predictors together. For example, Gene Set Enrichment Analysis (GSEA) considers the perturbation of whole (functionally related) gene sets rather than of single genes. These gene sets might be known biochemical pathways or otherwise functionally related genes. The advantage of this approach is that it is more robust: It is more likely that a single gene is found to be falsely perturbed than it is that a whole pathway is falsely perturbed. Furthermore, one can integrate the accumulated knowledge about biochemical pathways (like the
JAK-STAT signaling pathway The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumor formation. The pathway communicates information from chemical signals outs ...
) using this approach.


Bioinformatics advances in databases, data mining, and biological interpretation

The development of
biological database Biological databases are libraries of biological sciences, collected from scientific experiments, published literature, high-throughput experiment technology, and computational analysis. They contain information from research areas including geno ...
s enables storage and management of biological data with the possibility of ensuring access for users around the world. They are useful for researchers depositing data, retrieve information and files (raw or processed) originated from other experiments or indexing scientific articles, as
PubMed PubMed is an openly accessible, free database which includes primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institute ...
. Another possibility is search for the desired term (a gene, a protein, a disease, an organism, and so on) and check all results related to this search. There are databases dedicated to
SNPs In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in ...
(
dbSNP The Single Nucleotide Polymorphism Database (dbSNP) is a free public archive for genetic variation within and across different species developed and hosted by the National Center for Biotechnology Information (NCBI) in collaboration with the Natio ...
), the knowledge on genes characterization and their pathways (
KEGG KEGG (Kyoto Encyclopedia of Genes and Genomes) is a collection of databases dealing with genomes, biological pathways, diseases, drugs, and chemical substances. KEGG is utilized for bioinformatics research and education, including data analysis ...
) and the description of gene function classifying it by cellular component, molecular function and biological process (
Gene Ontology The Gene Ontology (GO) is a major bioinformatics initiative to unify the representation of gene and gene product attributes across all species. More specifically, the project aims to: 1) maintain and develop its controlled vocabulary of gene and ...
). In addition to databases that contain specific molecular information, there are others that are ample in the sense that they store information about an organism or group of organisms. As an example of a database directed towards just one organism, but that contains much data about it, is the ''
Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small plant from the mustard family (Brassicaceae), native to Eurasia and Africa. Commonly found along the shoulders of roads and in disturbed land, it is generally ...
'' genetic and molecular database – TAIR. Phytozome, in turn, stores the assemblies and annotation files of dozen of plant genomes, also containing visualization and analysis tools. Moreover, there is an interconnection between some databases in the information exchange/sharing and a major initiative was the
International Nucleotide Sequence Database Collaboration The International Nucleotide Sequence Database Collaboration (INSDC) consists of a joint effort to collect and disseminate databases containing DNA and RNA sequences. It involves the following computerized databases: NIG's DNA Data Bank of Japan ( ...
(INSDC) which relates data from DDBJ, EMBL-EBI, and NCBI. Nowadays, increase in size and complexity of molecular datasets leads to use of powerful statistical methods provided by computer science algorithms which are developed by
machine learning Machine learning (ML) is a field of study in artificial intelligence concerned with the development and study of Computational statistics, statistical algorithms that can learn from data and generalise to unseen data, and thus perform Task ( ...
area. Therefore, data mining and machine learning allow detection of patterns in data with a complex structure, as biological ones, by using methods of supervised and
unsupervised learning Unsupervised learning is a framework in machine learning where, in contrast to supervised learning, algorithms learn patterns exclusively from unlabeled data. Other frameworks in the spectrum of supervisions include weak- or semi-supervision, wh ...
, regression, detection of
clusters may refer to: Science and technology Astronomy * Cluster (spacecraft), constellation of four European Space Agency spacecraft * Cluster II (spacecraft), a European Space Agency mission to study the magnetosphere * Asteroid cluster, a small ...
and association rule mining, among others. To indicate some of them,
self-organizing map A self-organizing map (SOM) or self-organizing feature map (SOFM) is an unsupervised machine learning technique used to produce a low-dimensional (typically two-dimensional) representation of a higher-dimensional data set while preserving the t ...
s and ''k''-means are examples of cluster algorithms;
neural networks A neural network is a group of interconnected units called neurons that send signals to one another. Neurons can be either Cell (biology), biological cells or signal pathways. While individual neurons are simple, many of them together in a netwo ...
implementation and
support vector machine In machine learning, support vector machines (SVMs, also support vector networks) are supervised max-margin models with associated learning algorithms that analyze data for classification and regression analysis. Developed at AT&T Bell Laborato ...
s models are examples of common machine learning algorithms. Collaborative work among molecular biologists, bioinformaticians, statisticians and computer scientists is important to perform an experiment correctly, going from planning, passing through data generation and analysis, and ending with biological interpretation of the results.


Use of computationally intensive methods

On the other hand, the advent of modern computer technology and relatively cheap computing resources have enabled computer-intensive biostatistical methods like
bootstrapping In general, bootstrapping usually refers to a self-starting process that is supposed to continue or grow without external input. Many analytical techniques are often called bootstrap methods in reference to their self-starting or self-supporting ...
and re-sampling methods. In recent times,
random forests Random forests or random decision forests is an ensemble learning method for classification, regression and other tasks that works by creating a multitude of decision trees during training. For classification tasks, the output of the random for ...
have gained popularity as a method for performing
statistical classification When classification is performed by a computer, statistical methods are normally used to develop the algorithm. Often, the individual observations are analyzed into a set of quantifiable properties, known variously as explanatory variables or ''f ...
. Random forest techniques generate a panel of decision trees. Decision trees have the advantage that you can draw them and interpret them (even with a basic understanding of mathematics and statistics). Random Forests have thus been used for clinical decision support systems.


Applications


Public health

Public health Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the de ...
, including
epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...
,
health services research Health services research (HSR) became a burgeoning field in North America in the 1960s, when scientific information and policy deliberation began to coalesce. Sometimes also referred to as health systems research or health policy and systems resear ...
,
nutrition Nutrition is the biochemistry, biochemical and physiology, physiological process by which an organism uses food and water to support its life. The intake of these substances provides organisms with nutrients (divided into Macronutrient, macro- ...
,
environmental health Environmental health is the branch of public health concerned with all aspects of the natural environment, natural and built environment affecting human health. To effectively control factors that may affect health, the requirements for a hea ...
and health care policy & management. In these
medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...
contents, it's important to consider the design and analysis of the
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s. As one example, there is the assessment of severity state of a patient with a prognosis of an outcome of a disease. With new technologies and genetics knowledge, biostatistics are now also used for Systems medicine, which consists in a more personalized medicine. For this, is made an integration of data from different sources, including conventional patient data, clinico-pathological parameters, molecular and genetic data as well as data generated by additional new-omics technologies.


Quantitative genetics

The study of
population genetics Population genetics is a subfield of genetics that deals with genetic differences within and among populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as Adaptation (biology), adaptation, s ...
and
statistical genetics Statistical genetics is a scientific field concerned with the development and application of statistical methods for drawing inferences from genetic data. The term is most commonly used in the context of human genetics. Research in statistical ge ...
in order to link variation in
genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
with a variation in
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
. In other words, it is desirable to discover the genetic basis of a measurable trait, a quantitative trait, that is under polygenic control. A genome region that is responsible for a continuous trait is called a
quantitative trait locus A quantitative trait locus (QTL) is a locus (section of DNA) that correlates with variation of a quantitative trait in the phenotype of a population of organisms. QTLs are mapped by identifying which molecular markers (such as SNPs or AFLPs) ...
(QTL). The study of QTLs become feasible by using
molecular marker In molecular biology and other fields, a molecular marker is a molecule, sampled from some source, that gives information about its source. For example, DNA is a molecular marker that gives information about the organism from which it was taken. ...
s and measuring traits in populations, but their mapping needs the obtaining of a population from an experimental crossing, like an F2 or
recombinant inbred strain A recombinant inbred strain or recombinant inbred line (RIL) is an organism with chromosomes that incorporate an essentially permanent set of recombination events between chromosomes inherited from two or more inbred strains. F1 and F2 generations ...
s/lines (RILs). To scan for QTLs regions in a genome, a gene map based on linkage have to be built. Some of the best-known QTL mapping algorithms are Interval Mapping, Composite Interval Mapping, and Multiple Interval Mapping. However, QTL mapping resolution is impaired by the amount of recombination assayed, a problem for species in which it is difficult to obtain large offspring. Furthermore, allele diversity is restricted to individuals originated from contrasting parents, which limit studies of allele diversity when we have a panel of individuals representing a natural population. For this reason, the
genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different individuals to see if any variant is associated with a trait. GWA s ...
was proposed in order to identify QTLs based on
linkage disequilibrium Linkage disequilibrium, often abbreviated to LD, is a term in population genetics referring to the association of genes, usually linked genes, in a population. It has become an important tool in medical genetics and other fields In defining LD, it ...
, that is the non-random association between traits and molecular markers. It was leveraged by the development of high-throughput
SNP genotyping SNP genotyping is the measurement of genetic variations of single nucleotide polymorphisms (SNPs) between members of a species. It is a form of genotyping, which is the measurement of more general genetic variation. SNPs are one of the most commo ...
. In
animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...
and
plant breeding Plant breeding is the science of changing the traits of plants in order to produce desired characteristics. It is used to improve the quality of plant products for use by humans and animals. The goals of plant breeding are to produce crop varie ...
, the use of markers in
selection Selection may refer to: Science * Selection (biology), also called natural selection, selection in evolution ** Sex selection, in genetics ** Mate selection, in mating ** Sexual selection in humans, in human sexuality ** Human mating strat ...
aiming for breeding, mainly the molecular ones, collaborated to the development of
marker-assisted selection Marker assisted selection or marker aided selection (MAS) is an indirect selection process where a trait of interest is selected based on a marker ( morphological, biochemical or DNA/RNA variation) linked to a trait of interest (e.g. productivit ...
. While QTL mapping is limited due resolution, GWAS does not have enough power when rare variants of small effect that are also influenced by environment. So, the concept of Genomic Selection (GS) arises in order to use all molecular markers in the selection and allow the prediction of the performance of candidates in this selection. The proposal is to genotype and phenotype a training population, develop a model that can obtain the genomic estimated breeding values (GEBVs) of individuals belonging to a genotype and but not phenotype population, called testing population. This kind of study could also include a validation population, thinking in the concept of cross-validation, in which the real phenotype results measured in this population are compared with the phenotype results based on the prediction, what used to check the accuracy of the model. As a summary, some points about the application of quantitative genetics are: * This has been used in agriculture to improve crops (
Plant breeding Plant breeding is the science of changing the traits of plants in order to produce desired characteristics. It is used to improve the quality of plant products for use by humans and animals. The goals of plant breeding are to produce crop varie ...
) and
livestock Livestock are the Domestication, domesticated animals that are raised in an Agriculture, agricultural setting to provide labour and produce diversified products for consumption such as meat, Egg as food, eggs, milk, fur, leather, and wool. The t ...
(
Animal breeding Animal breeding is a branch of animal science that addresses the evaluation (using best linear unbiased prediction and other methods) of the genetic value (estimated breeding value, EBV) of livestock. Selecting for breeding animals with superior ...
). * In biomedical research, this work can assist in finding candidates
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
s that can cause or influence predisposition to diseases in
human genetics Human genetics is the study of inheritance as it occurs in Human, human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, populatio ...


Expression data

Studies for differential expression of genes from
RNA-Seq RNA-Seq (named as an abbreviation of RNA sequencing) is a technique that uses next-generation sequencing to reveal the presence and quantity of RNA molecules in a biological sample, providing a snapshot of gene expression in the sample, also k ...
data, as for RT-qPCR and
microarrays A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a solid substrate—usually a glass slide or silicon thin-film cell� ...
, demands comparison of conditions. The goal is to identify genes which have a significant change in abundance between different conditions. Then, experiments are designed appropriately, with replicates for each condition/treatment, randomization and blocking, when necessary. In RNA-Seq, the quantification of expression uses the information of mapped reads that are summarized in some genetic unit, as
exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...
s that are part of a gene sequence. As
microarray A microarray is a multiplex (assay), multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of biological interactions. It is a two-dimensional array on a Substrate (materials science), solid substrate—usu ...
results can be approximated by a normal distribution, RNA-Seq counts data are better explained by other distributions. The first used distribution was the Poisson one, but it underestimate the sample error, leading to false positives. Currently, biological variation is considered by methods that estimate a dispersion parameter of a
negative binomial distribution In probability theory and statistics, the negative binomial distribution, also called a Pascal distribution, is a discrete probability distribution that models the number of failures in a sequence of independent and identically distributed Berno ...
.
Generalized linear model In statistics, a generalized linear model (GLM) is a flexible generalization of ordinary linear regression. The GLM generalizes linear regression by allowing the linear model to be related to the response variable via a ''link function'' and by ...
s are used to perform the tests for statistical significance and as the number of genes is high, multiple tests correction have to be considered. Some examples of other analysis on
genomics Genomics is an interdisciplinary field of molecular biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, ...
data comes from microarray or
proteomics Proteomics is the large-scale study of proteins. Proteins are vital macromolecules of all living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replicatio ...
experiments. Often concerning diseases or disease stages.


Other studies

*
Ecology Ecology () is the natural science of the relationships among living organisms and their Natural environment, environment. Ecology considers organisms at the individual, population, community (ecology), community, ecosystem, and biosphere lev ...
,
ecological forecasting Ecological forecasting uses knowledge of physics, ecology and physiology, to predict how ecological populations, communities, or ecosystems will change in the future in response to environmental factors such as climate change. The goal of the approa ...
* Biological
sequence analysis In bioinformatics, sequence analysis is the process of subjecting a DNA, RNA or peptide sequence to any of a wide range of analytical methods to understand its features, function, structure, or evolution. It can be performed on the entire genome ...
*
Systems biology Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological system ...
for gene network inference or pathways analysis. *
Clinical research Clinical research is a branch of medical research that involves people and aims to determine the effectiveness (efficacy) and safety of medications, devices, diagnostic products, and treatment regimens intended for improving human health. The ...
and pharmaceutical development *
Population dynamics Population dynamics is the type of mathematics used to model and study the size and age composition of populations as dynamical systems. Population dynamics is a branch of mathematical biology, and uses mathematical techniques such as differenti ...
, especially in regards to
fisheries science Fisheries science is the academic discipline of managing and understanding fisheries. It is a multidisciplinary science, which draws on the disciplines of limnology, oceanography, freshwater biology, marine biology, meteorology, conservation, ...
. *
Phylogenetics In biology, phylogenetics () is the study of the evolutionary history of life using observable characteristics of organisms (or genes), which is known as phylogenetic inference. It infers the relationship among organisms based on empirical dat ...
and
evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
*
Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemistry, biochemical and physiology, physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or comb ...
*
Pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...
*
Neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the neuroanatomy, structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive ...


Tools

There are a lot of tools that can be used to do statistical analysis in biological data. Most of them are useful in other areas of knowledge, covering a large number of applications (alphabetical). Here are brief descriptions of some of them: * ASReml: Another software developed by VSNi that can be used also in R environment as a package. It is developed to estimate variance components under a general linear mixed model using restricted maximum likelihood (REML). Models with fixed effects and random effects and nested or crossed ones are allowed. Gives the possibility to investigate different variance-covariance matrix structures. * CycDesigN: A computer package developed by VSNi that helps the researchers create experimental designs and analyze data coming from a design present in one of three classes handled by CycDesigN. These classes are resolvable, non-resolvable, partially replicated and crossover designs. It includes less used designs the Latinized ones, as t-Latinized design. *
Orange Orange most often refers to: *Orange (fruit), the fruit of the tree species '' Citrus'' × ''sinensis'' ** Orange blossom, its fragrant flower ** Orange juice *Orange (colour), the color of an orange fruit, occurs between red and yellow in the vi ...
: A programming interface for high-level data processing, data mining and data visualization. Include tools for gene expression and genomics. * R: An
open source Open source is source code that is made freely available for possible modification and redistribution. Products include permission to use and view the source code, design documents, or content of the product. The open source model is a decentrali ...
environment and programming language dedicated to statistical computing and graphics. It is an implementation of S language maintained by CRAN. In addition to its functions to read data tables, take descriptive statistics, develop and evaluate models, its repository contains packages developed by researchers around the world. This allows the development of functions written to deal with the statistical analysis of data that comes from specific applications. In the case of Bioinformatics, for example, there are packages located in the main repository (CRAN) and in others, as Bioconductor. It is also possible to use packages under development that are shared in hosting-services as
GitHub GitHub () is a Proprietary software, proprietary developer platform that allows developers to create, store, manage, and share their code. It uses Git to provide distributed version control and GitHub itself provides access control, bug trackin ...
. * SAS: A data analysis software widely used, going through universities, services and industry. Developed by a company with the same name (
SAS Institute SAS Institute (or SAS, pronounced "sass") is an American multinational developer of analytics and artificial intelligence software based in Cary, North Carolina. SAS develops and markets a suite of analytics software ( also called SAS), which ...
), it uses
SAS language The SAS language is a fourth-generation computer programming language used for statistical analysis, created by Anthony James Barr at North Carolina State University North Carolina State University (NC State, North Carolina State, NC State ...
for programming. * PLA 3.0: Is a biostatistical analysis software for regulated environments (e.g. drug testing) which supports Quantitative Response Assays (Parallel-Line, Parallel-Logistics, Slope-Ratio) and Dichotomous Assays (Quantal Response, Binary Assays). It also supports weighting methods for combination calculations and the automatic data aggregation of independent assay data. *
Weka The weka, also known as the Māori hen or woodhen (''Gallirallus australis'') is a flightless bird species of the rail family. It is endemic to New Zealand. Some authorities consider it as the only extant member of the genus '' Gallirallus''. ...
: A
Java Java is one of the Greater Sunda Islands in Indonesia. It is bordered by the Indian Ocean to the south and the Java Sea (a part of Pacific Ocean) to the north. With a population of 156.9 million people (including Madura) in mid 2024, proje ...
software for
machine learning Machine learning (ML) is a field of study in artificial intelligence concerned with the development and study of Computational statistics, statistical algorithms that can learn from data and generalise to unseen data, and thus perform Task ( ...
and
data mining Data mining is the process of extracting and finding patterns in massive data sets involving methods at the intersection of machine learning, statistics, and database systems. Data mining is an interdisciplinary subfield of computer science and ...
, including tools and methods for visualization, clustering, regression, association rule, and classification. There are tools for cross-validation, bootstrapping and a module of algorithm comparison. Weka also can be run in other programming languages as Perl or R. *
Python (programming language) Python is a high-level programming language, high-level, general-purpose programming language. Its design philosophy emphasizes code readability with the use of significant indentation. Python is type system#DYNAMIC, dynamically type-checked a ...
image analysis, deep-learning, machine-learning *
SQL Structured Query Language (SQL) (pronounced ''S-Q-L''; or alternatively as "sequel") is a domain-specific language used to manage data, especially in a relational database management system (RDBMS). It is particularly useful in handling s ...
databases *
NoSQL NoSQL (originally meaning "Not only SQL" or "non-relational") refers to a type of database design that stores and retrieves data differently from the traditional table-based structure of relational databases. Unlike relational databases, which ...
*
NumPy NumPy (pronounced ) is a library for the Python programming language, adding support for large, multi-dimensional arrays and matrices, along with a large collection of high-level mathematical functions to operate on these arrays. The predeces ...
numerical python *
SciPy SciPy (pronounced "sigh pie") is a free and open-source Python library used for scientific computing and technical computing. SciPy contains modules for optimization, linear algebra, integration, interpolation, special functions, fast Fourier ...
*
SageMath SageMath (previously Sage or SAGE, "System for Algebra and Geometry Experimentation") is a computer algebra system (CAS) with features covering many aspects of mathematics, including algebra, combinatorics, graph theory, group theory, differentia ...
*
LAPACK LAPACK ("Linear Algebra Package") is a standard software library for numerical linear algebra. It provides routines for solving systems of linear equations and linear least squares, eigenvalue problems, and singular value decomposition. It als ...
linear algebra *
MATLAB MATLAB (an abbreviation of "MATrix LABoratory") is a proprietary multi-paradigm programming language and numeric computing environment developed by MathWorks. MATLAB allows matrix manipulations, plotting of functions and data, implementat ...
*
Apache Hadoop Apache Hadoop () is a collection of open-source software utilities for reliable, scalable, distributed computing. It provides a software framework for distributed storage and processing of big data using the MapReduce programming model. Hadoop wa ...
*
Apache Spark Apache Spark is an open-source unified analytics engine for large-scale data processing. Spark provides an interface for programming clusters with implicit data parallelism and fault tolerance. Originally developed at the University of Californ ...
*
Amazon Web Services Amazon Web Services, Inc. (AWS) is a subsidiary of Amazon.com, Amazon that provides Software as a service, on-demand cloud computing computing platform, platforms and Application programming interface, APIs to individuals, companies, and gover ...


Scope and training programs

Almost all educational programmes in biostatistics are at
postgraduate Postgraduate education, graduate education, or graduate school consists of academic or professional degrees, certificates, diplomas, or other qualifications usually pursued by post-secondary students who have earned an undergraduate (bachelor' ...
level. They are most often found in schools of public health, affiliated with schools of medicine, forestry, or agriculture, or as a focus of application in departments of statistics. In the United States, where several universities have dedicated biostatistics departments, many other top-tier universities integrate biostatistics faculty into statistics or other departments, such as
epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...
. Thus, departments carrying the name "biostatistics" may exist under quite different structures. For instance, relatively new biostatistics departments have been founded with a focus on
bioinformatics Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...
and
computational biology Computational biology refers to the use of techniques in computer science, data analysis, mathematical modeling and Computer simulation, computational simulations to understand biological systems and relationships. An intersection of computer sci ...
, whereas older departments, typically affiliated with schools of
public health Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the de ...
, will have more traditional lines of research involving epidemiological studies and
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s as well as bioinformatics. In larger universities around the world, where both a statistics and a biostatistics department exist, the degree of integration between the two departments may range from the bare minimum to very close collaboration. In general, the difference between a statistics program and a biostatistics program is twofold: (i) statistics departments will often host theoretical/methodological research which are less common in biostatistics programs and (ii) statistics departments have lines of research that may include biomedical applications but also other areas such as industry (
quality control Quality control (QC) is a process by which entities review the quality of all factors involved in production. ISO 9000 defines quality control as "a part of quality management focused on fulfilling quality requirements". This approach plac ...
), business and
economics Economics () is a behavioral science that studies the Production (economics), production, distribution (economics), distribution, and Consumption (economics), consumption of goods and services. Economics focuses on the behaviour and interac ...
and biological areas other than medicine.


Specialized journals

* Biostatistics * International Journal of Biostatistics * Journal of Epidemiology and Biostatistics * Biostatistics and Public Health * Biometrics * Biometrika * Biometrical Journal * Communications in Biometry and Crop Science * Statistical Applications in Genetics and Molecular Biology * Statistical Methods in Medical Research * Pharmaceutical Statistics * Statistics in Medicine


See also

*
Bioinformatics Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...
* Epidemiological method *
Epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and Risk factor (epidemiology), determinants of health and disease conditions in a defined population, and application of this knowledge to prevent dise ...
*
Group size measures Many animals, including humans, tend to live in groups, herds, flock (birds), flocks, bands, Pack (canine), packs, Shoaling and schooling, shoals, or Bird colony, colonies (hereafter: groups) of conspecific individuals. The size of these groups, as ...
*
Health indicator Health indicators are quantifiable characteristics of a population which researchers use as supporting evidence for describing the health of a population. Typically, researchers will use a survey methodology to gather information about a populati ...
*
Mathematical and theoretical biology Mathematical and theoretical biology, or biomathematics, is a branch of biology which employs theoretical analysis, mathematical models and abstractions of living organisms to investigate the principles that govern the structure, development ...


References


External links

*
The International Biometric Society

The Collection of Biostatistics Research Archive

Guide to Biostatistics (MedPageToday.com)

Biomedical Statistics
{{Authority control Bioinformatics