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Molecular pathological epidemiology (MPE, also molecular pathologic epidemiology) is a
discipline Discipline refers to rule following behavior, to regulate, order, control and authority. It may also refer to punishment. Discipline is used to create habits, routines, and automatic mechanisms such as blind obedience. It may be inflicted on ot ...
combining
epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidenc ...
and
pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
. It is defined as "epidemiology of
molecular pathology Molecular pathology is an emerging discipline within pathology which is focused in the study and diagnosis of disease through the examination of molecules within organs, tissues or bodily fluids. Molecular pathology shares some aspects of practice ...
and
heterogeneity Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, siz ...
of disease". Pathology and epidemiology share the same goal of elucidating
etiology Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
of disease, and MPE aims to achieve this goal at molecular, individual and population levels. Typically, MPE utilizes tissue pathology resources and data within existing epidemiology studies.
Molecular epidemiology Molecular epidemiology is a branch of epidemiology and medical science that focuses on the contribution of potential genetic and environmental risk factors, identified at the molecular level, to the etiology, distribution and prevention of disease ...
broadly encompasses MPE and conventional-type molecular epidemiology with the use of traditional disease designation systems.


Disease process

Data from
The Cancer Genome Atlas ''The'' () is a grammatical article in English, denoting persons or things already mentioned, under discussion, implied or otherwise presumed familiar to listeners, readers, or speakers. It is the definite article in English. ''The'' is the m ...
projects indicate that disease evolution is an inherently heterogeneous process. Each patient has a unique disease process (“the unique disease principle”), considering the uniqueness of the
exposome An environmental factor, ecological factor or eco factor is any factor, abiotic or biotic, that influences living organisms. Abiotic factors include ambient temperature, amount of sunlight, and pH of the water soil in which an organism lives. Bi ...
and its unique influence on molecular pathologic process. This concept has been adopted in clinical medicine along with
precision medicine Precision, precise or precisely may refer to: Science, and technology, and mathematics Mathematics and computing (general) * Accuracy and precision, measurement deviation from true value and its scatter * Significant figures, the number of digit ...
and
personalized medicine Personalized medicine, also referred to as precision medicine, is a medical model that separates people into different groups—with medical decisions, practices, interventions and/or products being tailored to the individual patient based on the ...
.


Methodology

In MPE, investigators dissect interrelationships between exposures (e.g., environmental, dietary, lifestyle and genetic factors); alterations in cellular or extracellular molecules (disease molecular signatures); and disease evolution and progression. Investigators can analyze
genome In the fields of molecular biology and genetics, 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 ge ...
,
methylome DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
,
epigenome An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome ...
,
metabolome The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The smal ...
,
transcriptome The transcriptome is the set of all RNA transcripts, including coding and non-coding, in an individual or a population of cells. The term can also sometimes be used to refer to all RNAs, or just mRNA, depending on the particular experiment. The t ...
,
proteome The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
,
microbiome A microbiome () is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps ''et al.'' as "a characteristic microbial community occupying a reasonably well ...
,
immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity desc ...
and
interactome In molecular biology, an interactome is the whole set of molecular interactions in a particular cell. The term specifically refers to physical interactions among molecules (such as those among proteins, also known as protein–protein interactions, ...
. A putative risk factor can be linked to specific molecular signatures. MPE research enables identification of a new
biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
for potential clinical utility, using large-scale population-based data (e.g., PIK3CA
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
in
colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
to select patients for
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
therapy). The MPE approach can be used following a
genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different i ...
(GWAS), termed "GWAS-MPE approach". Detailed disease endpoint phenotyping can be conducted by means of molecular pathology or surrogate
histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...
or
immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...
analysis of diseased tissues and cells within GWAS. As an alternative approach, potential risk variants identified by GWAS can be examined in combination with molecular pathology analysis on diseased tissues. This GWAS-MPE approach can give not only more precise effect estimates, even larger effects, for specific molecular subtypes of the disease, but also insights into pathogenesis by linking genetic variants to molecular pathologic signatures of disease. Since
molecular diagnostics Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome, and how their cells express their genes as proteins, applying molecular biology to medical testing. In medicine the technique is ...
is becoming routine clinical practice, molecular pathology data can aid epidemiologic research.


History

MPE began as analysis of risk factors (e.g., smoking) and molecular pathological findings (e.g., ''
KRAS ''KRAS'' (Kirsten rat sarcoma virus) is a gene that provides instructions for making a protein called K-Ras, a part of the RAS/MAPK pathway. The protein relays signals from outside the cell to the cell's nucleus. These signals instruct the cell ...
'' G12C
oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.
mutations in lung carcinoma). Studies to examine the relationship between an exposure and molecular pathological signatures of disease (particularly, cancer) became increasingly common throughout the 1990s and early 2000s. The use of molecular pathology in epidemiology lacked standardized methodologies and guidelines as well as interdisciplinary experts and training programs. MPE research required a new
conceptual framework A conceptual framework is an analytical tool with several variations and contexts. It can be applied in different categories of work where an overall picture is needed. It is used to make conceptual distinctions and organize ideas. Strong conceptu ...
and methodologies (
epidemiological method The science of epidemiology has matured significantly from the times of Hippocrates, Semmelweis and John Snow. The techniques for gathering and analyzing epidemiological data vary depending on the type of disease being monitored but each study will ...
) because MPE examines heterogeneity in an outcome variable. The term "molecular pathological epidemiology" was used by Shuji Ogino and Meir Stampfer in 2010. Specific principles of MPE developed following 2010. The MPE
paradigm In science and philosophy, a paradigm () is a distinct set of concepts or thought patterns, including theories, research methods, postulates, and standards for what constitute legitimate contributions to a field. Etymology ''Paradigm'' comes f ...
is in widespread use globally, and has been a subject of international conferences. The International Molecular Pathological Epidemiology (MPE) Meeting Series, which was established in 2013, has been open to the research community around the world, and five meetings were held through 2021.


See also


References


Further reading

* * * {{Biology-footer Epidemiology Pathology