|
Hit Selection
In high-throughput screening (HTS), one of the major goals is to select compounds (including small molecules, siRNAs, shRNA, genes, et al.) with a desired size of inhibition or activation effects. A compound with a desired size of effects in an HTS screen is called a hit. The process of selecting hits is called hit selection. Methods for hit selection in general HTS experiments have the ability to screen tens of thousands (or even millions) of compounds rapidly. Hence, it is a challenge to glean chemical/biochemical significance from mounds of data in the process of hit selection. To address this challenge, appropriate analytic methods have been adopted for hit selection. There are two main strategies of selecting hits with large effects. One is to use certain metric(s) to rank and/or classify the compounds by their effects and then to select the largest number of potent compounds that is practical for validation assays. The other strategy is to test whether a compound has effects s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
High-throughput Screening
High-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handling devices, and sensitive detectors, high-throughput screening allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests. Through this process one can quickly recognize active compounds, antibodies, or genes that modulate a particular biomolecular pathway. The results of these experiments provide starting points for drug design and for understanding the noninteraction or role of a particular location. Assay plate preparation The key labware or testing vessel of HTS is the microtiter plate, which is a small container, usually disposable and made of plastic, that features a grid of small, open divots called ''wells''. In general, microplates for HTS have either 96, 192, 384, 1536, 3456 or 6144 wells. The ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Small Molecule
Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs are small molecules; the terms are equivalent in the literature. Larger structures such as nucleic acids and proteins, and many polysaccharides are not small molecules, although their constituent monomers (ribo- or deoxyribonucleotides, amino acids, and monosaccharides, respectively) are often considered small molecules. Small molecules may be used as research tools to probe biological function as well as leads in the development of new therapeutic agents. Some can inhibit a specific function of a protein or disrupt protein–protein interactions. Pharmacology usually restricts the term "small molecule" to molecules that bind specific biological macromolecules and act as an effector, altering the activity or function of the target. Small ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SiRNA
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating within the RNA interference (RNAi) pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, preventing translation. Text was copied from this source, which is available under Creative Commons Attribution 4.0 International License Structure Naturally occurring siRNAs have a well-defined structure that is a short (usually 20 to 24- bp) double-stranded RNA (dsRNA) with phosphorylated 5' ends and hydroxylated 3' ends with two overhanging nucleotides. The Dicer enzyme catalyzes production of siRNAs from long dsRNAs and small hairpin RNAs. siRNAs can also be introduced into cells by transfection. Since in principle any gene can be knocked down by a syntheti ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ShRNA
A short hairpin RNA or small hairpin RNA (shRNA/Hairpin Vector) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors. shRNA is an advantageous mediator of RNAi in that it has a relatively low rate of degradation and turnover. However, it requires use of an expression vector, which has the potential to cause side effects in medicinal applications. The promoter choice is essential to achieve robust shRNA expression. At first, polymerase III promoters such as U6 and H1 were used; however, these promoters lack spatial and temporal control. As such, there has been a shift to using polymerase II promoters, which are inducible, to regulate shRNA expression. Delivery Expression of shRNA in cells can be obtained by delivery of plasmids or through viral or bacterial vectors. Delivery of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and 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: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemical Compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element is therefore not a compound. A compound can be transformed into a different substance by a chemical reaction, which may involve interactions with other substances. In this process, bonds between atoms may be broken and/or new bonds formed. There are four major types of compounds, distinguished by how the constituent atoms are bonded together. Molecular compounds are held together by covalent bonds; ionic compounds are held together by ionic bonds; intermetallic compounds are held together by metallic bonds; coordination complexes are held together by coordinate covalent bonds. Non-stoichiometric compounds form a disputed marginal case. A chemical formula specifies the number of atoms of each element in a compound molecule, using the s ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Assay
An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The measured entity is often called the analyte, the measurand, or the target of the assay. The analyte can be a drug, biochemical substance, chemical element or compound, or cell in an organism or organic sample. An assay usually aims to measure an analyte's intensive property and express it in the relevant measurement unit (e.g. molarity, density, functional activity in enzyme international units, degree of effect in comparison to a standard, etc.). If the assay involves exogenous reactants (the reagents), then their quantities are kept fixed (or in excess) so that the quantity and quality of the target are the only limiting factors. The difference in the assay outcome is used to deduce the unknown quality or quantity o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SSMD
In statistics, the strictly standardized mean difference (SSMD) is a measure of effect size. It is the mean divided by the standard deviation of a difference between two random values each from one of two groups. It was initially proposed for quality control and hit selection in high-throughput screening (HTS) and has become a statistical parameter measuring effect sizes for the comparison of any two groups with random values. Background In high-throughput screening (HTS), quality control (QC) is critical. An important QC characteristic in a HTS assay is how much the positive controls, test compounds, and negative controls differ from one another. This QC characteristic can be evaluated using the comparison of two well types in HTS assays. Signal-to-noise ratio (S/N), signal-to-background ratio (S/B), and the Z-factor have been adopted to evaluate the quality of HTS assays through the comparison of two investigated types of wells. However, the S/B does not take into account any in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dual-flashlight Plot
In statistics, a dual-flashlight plot is a type of scatter-plot in which the standardized mean of a contrast variable ( SMCV) is plotted against the mean of a contrast variable representing a comparison of interest . The commonly used dual-flashlight plot is for the difference between two groups in high-throughput experiments such as microarrays and high-throughput screening studies, in which we plot the SSMD versus average log fold-change on the ''y''- and ''x''-axes, respectively, for all genes or compounds (such as siRNAs or small molecules) investigated in an experiment. As a whole, the points in a dual-flashlight plot look like the beams of a flashlight with two heads, hence the name dual-flashlight plot. With the dual-flashlight plot, we can see how the genes or compounds are distributed into each category in effect sizes, as shown in the figure. Meanwhile, we can also see the average fold-change for each gene or compound. The dual-flashlight plot is similar to the volcano ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Effect Size
In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the value of a parameter for a hypothetical population, or to the equation that operationalizes how statistics or parameters lead to the effect size value. Examples of effect sizes include the correlation between two variables, the regression coefficient in a regression, the mean difference, or the risk of a particular event (such as a heart attack) happening. Effect sizes complement statistical hypothesis testing, and play an important role in power analyses, sample size planning, and in meta-analyses. The cluster of data-analysis methods concerning effect sizes is referred to as estimation statistics. Effect size is an essential component when evaluating the strength of a statistical claim, and it is the first item (magnitude) in the MAGI ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Z-score
In statistics, the standard score is the number of standard deviations by which the value of a raw score (i.e., an observed value or data point) is above or below the mean value of what is being observed or measured. Raw scores above the mean have positive standard scores, while those below the mean have negative standard scores. It is calculated by subtracting the population mean from an individual raw score and then dividing the difference by the population standard deviation. This process of converting a raw score into a standard score is called standardizing or normalizing (however, "normalizing" can refer to many types of ratios; see normalization for more). Standard scores are most commonly called ''z''-scores; the two terms may be used interchangeably, as they are in this article. Other equivalent terms in use include z-values, normal scores, standardized variables and pull in high energy physics. Computing a z-score requires knowledge of the mean and standard devi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SMCV
In statistics, the standardized mean of a contrast variable (SMCV or SMC), is a parameter assessing effect size. The SMCV is defined as mean divided by the standard deviation of a contrast variable. The SMCV was first proposed for one-way ANOVA cases and was then extended to multi-factor ANOVA cases . Background Consistent interpretations for the strength of group comparison, as represented by a contrast, are important. When there are only two groups involved in a comparison, SMCV is the same as the strictly standardized mean difference (SSMD). SSMD belongs to a popular type of effect-size measure called "standardized mean differences" which includes Cohen's d and Glass's \delta. In ANOVA, a similar parameter for measuring the strength of group comparison is standardized effect size (SES). One issue with SES is that its values are incomparable for contrasts with different coefficients. SMCV does not have such an issue. Concept Suppose the random values in t group ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
