Removing Gap Columns from MSA

BY IN Code, Python, Tutorials NO COMMENTS YET ,

Consider the following multiple sequence alignment: >HUMAN —————–METTNGT-ETWYESLHAVLKALNATLHSNLLCRPGPGL–G– >MOUSE —————–METSNGT-ETWYMSLHAVLKALNTTLHSHLLCRPGPGP–G– >CHICKEN —————–MEEDNRT-EPWHHSLQAMLDALNQTLHRAILHP-ST——- … Let’s say you want to remove the columns from the alignment where the query (human) protein sequence has a gap. You may want to do this for a number of reasons though I had to do this trick to get my local

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The Use of Orthologous Sequences to Predict the Impact of Amino Acid Substitutions on Protein Function

BY IN Comparative genomics, Functional impact prediction, Journal Club NO COMMENTS YET , ,

For nonsynonymous coding variants, functional impact prediction algorithms frequently make use of conservation of amino acid substitutions observed among homologous proteins at a given site under the assumption substitutions occurring at well-conserved sites will deleteriously impact protein function and substitutions occurring at less conserved sites will be tolerated. In this study, Marini et al. examine

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In silico analysis of missense substitutions using sequence-alignment based methods

BY IN Functional impact prediction, Journal Club, Review NO COMMENTS YET , , , , , , , ,

Computational classifiers classify missense substitutions as pathogenetic or neutral based on inferences from evolutionary conservation using protein multiple sequence alignments (PMSAs) of the gene of interest (and other features). In this review, Tavtigian et al. make suggestions with respect to the important aspects of creating PMSAs that are informative for classification (and more). In using

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Sequence variation in G-protein-coupled receptors: analysis of single nucleotide polymorphisms

BY IN Functional impact prediction, Journal Club, Machine learning NO COMMENTS YET , , , , , , , ,

G-protein-coupled receptors (GPCRs) play an important role in many physiological processes such as signal transduction and are frequently the targets for the majority of prescription drugs such as beta-blockers and anti-histamines. Understanding the role of sequence variations such as SNPs in GPCRs has potential implications for elucidating disease pathogenesis mechanisms and drug efficacy issues. In

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Prediction of Missense Mutation Functionality Depends on Both the Algorithm and Sequence Alignment Employed

BY IN Functional impact prediction, Journal Club 1 COMMENT , , , , , , , , ,

A number of algorithms have been developed to predict the impact of missense mutations on protein structure and function using sequence and structure-based approaches, notably SIFT, PolyPhen-2, Xvar, and Align-GVGD. In this study, Hicks et al. demonstrate that accurately predicting the impact of missense mutations on protein function depends on the algorithm used, the type

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