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Epistasis Analysis

Epistasis Analysis

Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...

Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion

Pharmacokinetics in Obese Patients: Drug Metabolism and Excretion

Drug metabolism, a critical process in the liver, involves two primary phases: Phase I reactions and Phase II conjugation. Obesity introduces significant alterations in this metabolic process, primarily due to fatty infiltration of the liver, leading to conditions such as nonalcoholic fatty liver disease (NAFLD). This condition can modify the activities of both Phase I and II enzymes, impacting how drugs are metabolized in obese patients.Phase I metabolism sees variable effects across...

Epistasis

Epistasis

In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...

Pharmacogenetics of Drug Metabolism: Overview

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...

Regulation of Metabolism

Regulation of Metabolism

Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...

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Related Experiment Video

Updated: Jun 11, 2026

Stable Isotope In-Vivo Labeling for Mass-Spectrometry Identification of Paternal Metabolites Transferred from Sperm to Oocyte During Fertilization

Stable Isotope In-Vivo Labeling for Mass-Spectrometry Identification of Paternal Metabolites Transferred from Sperm to Oocyte During Fertilization

Published on: June 17, 2025

Deep epistasis in human metabolism.

Marcin Imielinski¹, Calin Belta

¹Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. mimielinski@partners.org

Chaos (Woodbury, N.Y.)

|July 2, 2010

Summary

We developed a new method to uncover complex gene interactions in human metabolism. This approach identifies numerous gene combinations that disrupt key metabolic functions, revealing significant pathway redundancy.

Area of Science:

Biochemistry
Systems Biology
Genomics

Background:

Understanding complex gene interactions (epistasis) is crucial for deciphering metabolic functions.
Previous methods were limited in analyzing high-order epistasis in large-scale biological networks.

Purpose of the Study:

To apply a novel method for deriving high-order epistatic relationships in human metabolism.
To identify synergistic gene knockout sets that disable critical metabolic functions.
To investigate pathway redundancy and parallelism in human metabolic networks.

Main Methods:

Extended and applied a developed method for high-order epistasis analysis.
Utilized a published genome-scale model of human metabolism.
Computed 33,328 reaction sets for synergistic knockouts impacting 43 metabolic functions.

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Last Updated: Jun 11, 2026

Stable Isotope In-Vivo Labeling for Mass-Spectrometry Identification of Paternal Metabolites Transferred from Sperm to Oocyte During Fertilization

Stable Isotope In-Vivo Labeling for Mass-Spectrometry Identification of Paternal Metabolites Transferred from Sperm to Oocyte During Fertilization

Published on: June 17, 2025

The MPLEx Protocol for Multi-omic Analyses of Soil Samples

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A Zebrafish Model of Diabetes Mellitus and Metabolic Memory

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Designed minimal knockouts targeting fumarase flux.

Main Results:

Identified numerous reaction sets (33,328) causing synergistic disruption of metabolic functions.
Discovered extensive pathway parallelism and deep epistasis among diverse genes.
Demonstrated minimal knockouts for fumarase, an enzyme implicated in human cancer.
Showcased that effective knockout sets often involve >8 buffering reactions across compartments and subsystems.

Conclusions:

Human metabolic pathways exhibit significant parallelism and redundancy.
The findings suggest deep epistasis between genes with diverse annotations.
Results provide a basis for experimental validation of pathway redundancy via chemical and genetic perturbations.
The study opens avenues for future statistical analyses of epistasis in genetic variation data.