Month: November 2016


[PMID:27892959] [Nature Methods]

novoBreak: local assembly for breakpoint detection in cancer genomes

“a genome-wide local assembly algorithm that discovers somatic and germline structural variation breakpoints in whole-genome sequencing data.” “it more effectively utilized reads spanning breakpoints. novoBreak also demonstrated great sensitivity in identifying short insertions and deletions.” “For a 40× 2 × 101 bp whole-genome tumor and normal pairs, novoBreak needs a main memory less than 40 GB and a running time less than ~6 h with 10 CPU cores.”


[PMID:27866706] [American Journal of Human Genetics]

Colocalization of GWAS and eQTL Signals Detects Target Genes

“Identifying whether or not the same variant is causal in both GWASs and expression quantitative trail locus (eQTL) studies is challenging because of the uncertainty induced by linkage disequilibrium and the fact that some loci harbor multiple causal variants. However, current methods that address this problem assume that each locus contains a single causal variant.” “PrediXscan and TWAS, which impute gene expression and then associate the imputed expression with the trait, are examples of such methods. However, these methods do not provide a basis for determining colocalization of GWAS causal variants and eQTL causal variants.”

T Cell Infiltration Scores in TCGA

[PMID:27855702] [Genome Biology]

Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures 

“a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types.” “clear cell renal cell carcinoma (ccRCC) is among the highest for both scores.” “the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM).”

EmVar and EmVClass

[PMID:27843123] [American Journal of Human Genetics]

Reassessment of Genomic Sequence Variation to Harmonize Interpretation for Personalized Medicine

“EmVar (formerly known as EmBase) is the database in which variants identified in our molecular diagnostic laboratory are captured and classified.” “De-identified data from EmVar can be viewed online in EmVClass, which is an open-access resource.” From Emory Genetics Laboratory (EGL).

Mutational Profiling in POETIC Multiple Biopsies

[PMID:27827358] [Nature Communications]

Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation

“We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.” “Single-nucleotide variants were detected using the union of three callers”, union for SNVs — I vote for intersection, VarScan has too many calls… “InDels were detected using the union of four callers”, again, union here.

Pooled Functional Assay for All Missense Variants in a Gene

[PMID:27749844] [Nature Genetics]

Prospective functional classification of all possible missense variants in PPARG

“To prospectively characterize PPARγvariants, we used highly parallel oligonucleotide synthesis to construct a library encoding all 9,595 possible single–amino acid substitutions. We developed a pooled functional assay in human macrophages, experimentally evaluated all protein variants, and used the experimental data to train a variant classifier by supervised machine learning.” Work from David Altshuler.