Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Viral Mutations

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...

Phylogeny

Phylogeny

Phylogeny is concerned with the evolutionary diversification of organisms or groups of organisms. A group of organisms with a name is called a taxon (singular). Taxa (plural) can span different levels of the evolutionary hierarchy. For instance, the group containing all birds is a taxon (comprising the class Aves), and the group of all species of daisies (the genus Bellis) is a taxon. Phylogenies can likewise include just one genus (i.e., depict species relationships) or span an entire kingdom.

Pleiotropy

Pleiotropy

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,...

Cystic Fibrosis: Pathogenesis

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...

Phylogenetic Trees

Phylogenetic Trees

Phylogenetic trees come in many forms. It matters in which sequence the organisms are arranged from the bottom to the top of the tree, but the branches can rotate at their nodes without altering the information. The lines connecting individual nodes can be straight, angled, or even curved.

Mismatch Repair

Mismatch Repair

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...

You might also read

Related Articles

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

Sort by

Same author

Conserved 3D genome reorganization during DNA repair.

Life science alliance·2025

Same author

Genome-wide strand-specific UV mutagenesis in <i><i>Escherichia coli</i></i> is directed by the Mfd translocase.

Proceedings of the National Academy of Sciences of the United States of America·2025

Same author

Chromatin context shapes DNA damage formation and nucleotide excision repair dynamics in Caenorhabditis elegans.

Nucleic acids research·2025

Same author

DARKIN: a zero-shot benchmark for phosphosite-dark kinase association using protein language models.

Bioinformatics (Oxford, England)·2025

Same author

PHACE: Phylogeny-Aware Detection of Molecular Coevolution.

Molecular biology and evolution·2025

Same author

Insights Into Disability and Disability Progression in People With Multiple Sclerosis Using Large-Scale Healthcare Data.

European journal of neurology·2025

Search research articles

Related Experiment Video

Updated: Jun 22, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

PHACTboost: A Phylogeny-Aware Pathogenicity Predictor for Missense Mutations via Boosting.

Onur Dereli¹, Nurdan Kuru¹, Emrah Akkoyun^1,2

¹Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul 34956, Turkey.

Molecular Biology and Evolution

|June 27, 2024

Summary

This summary is machine-generated.

PHACTboost, a new tool, accurately predicts missense mutation pathogenicity by integrating evolutionary data. It outperforms existing methods, aiding genetic disease understanding and diagnosis.

Keywords:

Mendelian diseases amino acid substitution gradient boosting machine learning pathogenicity scoring phylogenetics

More Related Videos

In Vivo Modeling of the Morbid Human Genome using Danio rerio

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

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

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

Published on: August 20, 2019

Related Experiment Videos

Last Updated: Jun 22, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

In Vivo Modeling of the Morbid Human Genome using Danio rerio

In Vivo Modeling of the Morbid Human Genome using Danio rerio

Published on: August 24, 2013

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

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

Published on: August 20, 2019

Area of Science:

Genomics
Bioinformatics
Computational Biology

Background:

Pathogenicity prediction algorithms often rely solely on multiple sequence alignments, neglecting evolutionary context.
Phylogenetic trees offer a richer evolutionary perspective for variant effect prediction.

Purpose of the Study:

To introduce PHACTboost, a novel gradient boosting tree-based classifier for missense mutation pathogenicity prediction.
To enhance variant effect prediction by integrating multiple data sources including phylogenetic information.

Main Methods:

PHACTboost combines PHACT scores with multiple sequence alignments, phylogenetic trees, and ancestral reconstruction.
A gradient boosting tree approach was employed for classification.
Performance was evaluated against 40 existing pathogenicity predictors on curated variant datasets.

Main Results:

PHACTboost demonstrates superior performance compared to its predecessor, PHACT.
It outperforms 40 established pathogenicity predictors, including deep learning and recent tools like AlphaMissense, EVE, and CPT-1.
PHACTboost shows particular strength in classifying difficult variants where other predictors conflict.

Conclusions:

PHACTboost represents a significant advancement in missense mutation pathogenicity prediction.
Its ability to integrate diverse evolutionary data improves accuracy, especially for challenging variants.
The tool offers valuable predictions for millions of amino acid alterations, supporting genetic disease research and clinical diagnostics.