Tag: Variant Annotation

Human Noncoding Genome

[PMID: 29483654] [Nature Genetics]

The human noncoding genome defined by genetic diversity

“11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. ” “defined the context-dependent tolerance score (CDTS) as the absolute difference of the observed variation from the expected variation. “



[PMID: 29272339] [Bioinformatics]

Personal Cancer Genome Reporter: variant interpretation report for precision oncology  

“The Personal Cancer Genome Reporter (PCGR) is a stand-alone software package for functional annotation and translation of individual cancer genomes for precision oncology. It interprets both somatic SNVs/InDels and copy number aberrations. The software extends basic gene and variant annotations from the Ensembl’s Variant Effect Predictor (VEP) with oncology-relevant, up-to-date annotations retrieved flexibly through vcfanno, and produces interactive HTML reports intended for clinical interpretation.”

Performance of Variant Annotators in Clinical Use

[PMID: 29179779] [Genome Biology]

Evaluation of in silico algorithms for use with ACMG/AMP clinical variant interpretation guidelines

“compared performance of 25 algorithms” on “14,819 benign or pathogenic missense variants from the ClinVar”



[PMID: 28977528] [Nucleic Acids Research]

MAPPIN: a method for annotating, predicting pathogenicity and mode of inheritance for nonsynonymous variants

“a prediction method which utilizes a random forest algorithm to distinguish between nsSNVs with dominant, recessive, and benign effects.” “MAPPIN outperforms CADD and Eigen in predicting disease inheritance modes for all validation datasets. “



[PMID: 28851873] [Nature Communications]

Using ALoFT to determine the impact of putative loss-of-function variants in protein-coding genes

“Here, we present ALoFT (annotation of loss-of-function transcripts), a method to annotate and predict the disease-causing potential of loss-of-function variants. Using data from Mendelian disease-gene discovery projects, we show that ALoFT can distinguish between loss-of-function variants that are deleterious as heterozygotes and those causing disease only in the homozygous state. Investigation of variants discovered in healthy populations suggests that each individual carries at least two heterozygous premature stop alleles that could potentially lead to disease if present as homozygotes. ” Work from Daniel MacArthur & Mark Gerstein.



[PMID: 28522612] [Genome Research]

GenomeVIP: a cloud platform for genomic variant discovery and interpretation

“an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure.” Work from Li Ding.



[PMID:28416821] [Nature Genetics]

Pathogenic variants that alter protein code often disrupt splicing

“We discovered that the alleles causing splicing defects cluster in disease-associated genes (for example, haploinsufficient genes). We analyzed 4,964 published disease-causing exonic mutations using a massively parallel splicing assay (MaPSy), which showed an 81% concordance rate with splicing in patient tissue. Approximately 10% of exonic mutations altered splicing, mostly by disrupting multiple stages of spliceosome assembly.”