Monthly Archive: December 2018

Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins

Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins

Shai Carmi et. al., Nature Communications volume 5, Article number: 4835 (2014)

Abstract

The Ashkenazi Jewish (AJ) population is a genetic isolate close to European and Middle Eastern groups, with genetic diversity patterns conducive to disease mapping. Here we report high-depth sequencing of 128 complete genomes of AJ controls. Compared with European samples, our AJ panel has 47% more novel variants per genome and is eightfold more effective at filtering benign variants out of AJ clinical genomes. Our panel improves imputation accuracy for AJ SNP arrays by 28%, and covers at least one haplotype in ≈67% of any AJ genome with long, identical-by-descent segments. Reconstruction of recent AJ history from such segments confirms a recent bottleneck of merely ≈350 individuals. Modelling of ancient histories for AJ and European populations using their joint allele frequency spectrum determines AJ to be an even admixture of European and likely Middle Eastern origins. We date the split between the two ancestral populations to ≈12–25 Kyr, suggesting a predominantly Near Eastern source for the repopulation of Europe after the Last Glacial Maximum.

pdf, suppl

Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes

Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes
Mark D M Leiserson et. al., Nature Genetics volume 47, pages 106–114 (2015)

Abstract

Cancers exhibit extensive mutational heterogeneity, and the resulting long-tail phenomenon complicates the discovery of genes and pathways that are significantly mutated in cancer. We perform a pan-cancer analysis of mutated networks in 3,281 samples from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a new algorithm to find mutated subnetworks that overcomes the limitations of existing single-gene, pathway and network approaches. We identify 16 significantly mutated subnetworks that comprise well-known cancer signaling pathways as well as subnetworks with less characterized roles in cancer, including cohesin, condensin and others. Many of these subnetworks exhibit co-occurring mutations across samples. These subnetworks contain dozens of genes with rare somatic mutations across multiple cancers; many of these genes have additional evidence supporting a role in cancer. By illuminating these rare combinations of mutations, pan-cancer network analyses provide a roadmap to investigate new diagnostic and therapeutic opportunities across cancer types.

pdf, suppl

Links for Dec 2018

Frank Wilhoit: The Travesty of Liberalism
Conservatism consists of exactly one proposition, to wit:
There must be in-groups whom the law protectes but does not bind, alongside out-groups whom the law binds but does not protect.

Silicon Valley’s Chinese Dream: Tech elites, weary of democracy, look to the East by Jacob Silverman
Trump Fans Sink Savings Into ‘Iraqi Dinar’ Scam

An Alternative History of Silicon Valley Disruption

   “Temp: How American Work, American Business, and the American Dream Became Temporary’ by Louis Hyman
   “The Value of Everything: Making and Taking in the Global Economy” by Mariana Mazzucato
   “Winners Take All: The Elite Charade of Changing the World” by Anand Giridharadas

Create a living will without a lawyer

Interpreting 23andMe, Ancestry SNP array results: Promethease, SNPedia
Four Days Trapped at Sea With Crypto’s Nouveau Riche by Laurie Penny