Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

60
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
60
Pleiotropy01:33

Pleiotropy

43.7K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.7K
Mismatch Repair01:20

Mismatch Repair

6.8K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
6.8K
Mutations01:39

Mutations

95.1K
Overview
95.1K
Mutations01:35

Mutations

44.9K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.9K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

18.8K
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
18.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

An integrated, scaled approach to resolve TSC2 variants of uncertain significance.

Nature communications·2026
Same author

Saturation Genome Editing reveals the functional impact of RAD51D <i>and</i> XRCC2 variants.

bioRxiv : the preprint server for biology·2026
Same author

Improving splice site usage prediction with SPLAIRE.

bioRxiv : the preprint server for biology·2026
Same author

A Genome-First Study of Familial Hypercholesterolemia Comparing African and European Ancestry Individuals.

Circulation·2026
Same author

On the state of protein function prediction: a report on the fourth CAFA challenge.

bioRxiv : the preprint server for biology·2026
Same author

Gene- and domain-aware calibration increases the clinical utility of variant effect predictors.

Research square·2026

Related Experiment Video

Updated: Mar 2, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

14.4K

Missense variant pathogenicity predictors generalize well across a range of function-specific prediction challenges.

Vikas Pejaver1, Sean D Mooney2, Predrag Radivojac1

  • 1Department of Computer Science and Informatics, Indiana University, Bloomington, Indiana.

Human Mutation
|May 17, 2017
PubMed
Summary

Computational models predict missense variant impact, but their application differs. This study evaluated general pathogenicity predictors on specific protein function challenges, finding them effective for modeling mutation effects on protein function.

Keywords:
CAGI, functional effect prediction, generalization, machine learning, MutPredMutPred2, pathogenicity prediction, severity

More Related Videos

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

1.6K
In Vivo Modeling of the Morbid Human Genome using Danio rerio
12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

21.4K

Related Experiment Videos

Last Updated: Mar 2, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

14.4K
Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

1.6K
In Vivo Modeling of the Morbid Human Genome using Danio rerio
12:31

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

21.4K

Area of Science:

  • Computational biology
  • Genomics
  • Machine learning in bioinformatics

Background:

  • Machine learning and biomedical data advances enable missense variant impact assessment.
  • Existing computational models differ in operationalizing variant impact, focusing on pathogenicity or protein function effects.
  • The distinction and overlap between predicting variant pathogenicity and function alteration remain unclear.

Purpose of the Study:

  • To empirically assess the performance of computational methods in predicting missense variant impact.
  • To compare MutPred family methods against state-of-the-art approaches in protein-specific challenges.
  • To investigate the utility of general pathogenicity predictors for classifying function-altering variants without retraining.

Main Methods:

  • Participation in protein-specific challenges within the Critical Assessment of Genome Interpretation (CAGI) experiment.
  • Evaluation of MutPred family predictors and general-purpose pathogenicity predictors.
  • Comparison of predictor performance against experimental outcomes and other state-of-the-art methods.

Main Results:

  • MutPred family pathogenicity predictors demonstrated competitive performance against existing methods.
  • Predicted score distributions aligned with experimental outcomes for variant impact.
  • General pathogenicity predictors showed applicability to classifying specific function-altering variants.

Conclusions:

  • Binary classifiers trained on disease-causing mutations can effectively model biological aspects of mutation impact.
  • These models are capable of capturing the alteration of protein function resulting from mutations.
  • General pathogenicity predictors show promise for specific variant function classification tasks.