Month: September 2016

a-DMR in GWAS SNP LD Blocks

[PMID:27663977] [Genome Biology]

Novel regional age-associated DNA methylation changes within human common disease-associated loci

“In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19–82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue. This included 52 novel regions, 29 within loci not covered by 450 k or 27 k Illumina array, and with enrichment for DNase-I Hypersensitivity sites across the full range of tissues. These age-associated differentially methylated regions also show marked enrichment for enhancers and poised promoters across multiple cell types. In a replication set of 2084 DNA methylomes, 95.7 % of the age-associated differentially methylated regions showed the same direction of ageing effect”



[PMID:27659451] [Bioinformatics]

PSSV: A novel pattern-based probabilistic approach for somatic structural variation identification

“a novel pattern-based probabilistic approach, PSSV, to identify somatic structural variations from WGS data. PSSV features a mixture model with hidden states representing different mutation patterns; PSSV can thus differentiate heterozygous and homozygous SVs in each sample, enabling the identification of those somatic SVs with heterozygous mutations in normal samples and homozygous mutations in tumor samples.”

Breast Cancer Mutation and Immune Signatures

[PMID:27666519] [Nature Communications]

Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

“while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.”

APOBEC3 Germline Variants vs APOBEC-signature

[PMID:27643540] [Nature Genetics]

Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors

“SNP rs1014971 was associated with bladder cancer risk, increased APOBEC3B expression, and enrichment with APOBEC-signature mutations in bladder tumors. In contrast, a 30-kb deletion that eliminates APOBEC3B and creates anAPOBEC3AAPOBEC3B chimera was not important in bladder cancer, whereas it was associated with breast cancer risk and enrichment with APOBEC-signature mutations in breast tumors.”