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Updated: May 10, 2026

Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry CCMS

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Published on: December 20, 2010

MutationAssessor in cBioPortal.

Yang Su¹, Xiang Li², Boris Reva³

¹Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

Biorxiv : the Preprint Server for Biology

|August 20, 2025

Summary

This summary is machine-generated.

MutationAssessor (MA) version 4 refines functional impact scoring for cancer mutations. It enhances analysis of protein conservation and variant pathogenicity, aiding cancer genomics research.

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An Integrated Approach for Microprotein Identification and Sequence Analysis

An Integrated Approach for Microprotein Identification and Sequence Analysis

Published on: July 12, 2022

Area of Science:

Genomics
Bioinformatics
Computational Biology

Background:

Somatic and germline mutations in cancer require functional impact assessment.
MutationAssessor (MA) provides an evolution-based functional impact score (FIS) for mutations.
FIS scores leverage conservation patterns in protein families and subfamilies.

Purpose of the Study:

To introduce version 4 (r4) of MutationAssessor with significant improvements.
To refine the analysis of protein conservation patterns and sequence alignments.
To validate predicted functional impacts against curated variant databases and germline frequencies.

Main Methods:

Refined combinatorial entropy analysis of conservation patterns.
Recalculated full-length protein multiple sequence alignments using extensive sequence data.
Comparison of predicted functional impact with ClinVar classifications.
Analysis of variant frequency in germline genome sequences.
Exploration of switch-of-function mutational effects.

Main Results:

Enhanced accuracy in predicting the functional impact of cancer mutations.
Validation of FIS scores against known pathogenic and benign variants.
Observed inverse correlation between high functional impact and germline variant frequency.
Availability of functional impact data for ~4 million somatic mutations in cBioPortal.

Conclusions:

MutationAssessor r4 offers a robust tool for evaluating the functional consequences of cancer mutations.
The updated FIS provides valuable insights into mutation pathogenicity and evolutionary conservation.
The integration of MA data into cBioPortal facilitates cancer genomics research and clinical interpretation.