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Genetic Variation

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MET Exon 14 Skipping: A Case Study for the Detection of Genetic Variants in Cancer Driver Genes by Deep Learning.

International journal of molecular sciences
BACKGROUND: Disruption of alternative splicing (AS) is frequently observed in cancer and might represent an important signature for tumor progression and therapy. Exon skipping (ES) represents one of the most frequent AS events, and in non-small cell...

Opportunities and challenges for the computational interpretation of rare variation in clinically important genes.

American journal of human genetics
Genome sequencing is enabling precision medicine-tailoring treatment to the unique constellation of variants in an individual's genome. The impact of recurrent pathogenic variants is often understood, however there is a long tail of rare genetic vari...

A Deep-Learning Sequence-Based Method to Predict Protein Stability Changes Upon Genetic Variations.

Genes
Several studies have linked disruptions of protein stability and its normal functions to disease. Therefore, during the last few decades, many tools have been developed to predict the free energy changes upon protein residue variations. Most of these...

Application of the random forest algorithm to Streptococcus pyogenes response regulator allele variation: from machine learning to evolutionary models.

Scientific reports
Group A Streptococcus (GAS) is a globally significant bacterial pathogen. The GAS genotyping gold standard characterises the nucleotide variation of emm, which encodes a surface-exposed protein that is recombinogenic and under immune-based selection ...

Assigning function to SNPs: Considerations when interpreting genetic variation.

Seminars in cell & developmental biology
Assigning function to single nucleotide polymorphisms (SNPs) to understand the mechanisms that link genetic and phenotypic variation and disease is an area of intensive research that is necessary to contribute to the continuing development of precisi...

Machine learning-based identification and characterization of 15 novel pathogenic SUOX missense mutations.

Molecular genetics and metabolism
Isolated sulfite oxidase deficiency (ISOD) is a rare hereditary metabolic disease caused by absence of functional sulfite oxidase (SO) due to mutations of the SUOX gene. SO oxidizes toxic sulfite and sulfite accumulation is associated with neurologic...

Evolutionarily informed machine learning enhances the power of predictive gene-to-phenotype relationships.

Nature communications
Inferring phenotypic outcomes from genomic features is both a promise and challenge for systems biology. Using gene expression data to predict phenotypic outcomes, and functionally validating the genes with predictive powers are two challenges we add...

Revisiting the out of Africa event with a deep-learning approach.

American journal of human genetics
Anatomically modern humans evolved around 300 thousand years ago in Africa. They started to appear in the fossil record outside of Africa as early as 100 thousand years ago, although other hominins existed throughout Eurasia much earlier. Recently, s...

WEVar: a novel statistical learning framework for predicting noncoding regulatory variants.

Briefings in bioinformatics
Understanding the functional consequence of noncoding variants is of great interest. Though genome-wide association studies or quantitative trait locus analyses have identified variants associated with traits or molecular phenotypes, most of them are...