Research highlights

Type 2 Diabetes is known to have a strong genetic component. GWAS analyses have found several associated, relatively common variants (>5% frequency). A huge study looking at WES, low coverage WGS, and SNP data has found very little else. There had been the hope of finding “synthetic association”, i.e. the idea that common GWAS SNP signals come from nearby rare causal variants in linkage disequilibrium. But they found very limited evidence for the role of rare variants in Type 2 Diabetes. An accessible write-up: http://massgenomics.org/2016/07/genetic-architecture-complex-disease.html. The original paper: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature18642.html

Money from the ice bucket challenge has helped find some genetic underpinnings to ALS, otherwise known as Motor Neuron disease, and with Steven Hawking being a patient. Two papers: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3622.html, and http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3626.html. NYT write-up: http://www.nytimes.com/2016/07/28/health/the-ice-bucket-challenge-helped-scientists-discover-a-new-gene-tied-to-als.html

Circulating tumor DNA is ~20bp shorter than other circulating DNA, which may help the sensitivity of assays: http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006162

A new reference genome for the Qatari population (called QTRG), which produces ~750,000 fewer variants compared to the standard reference: http://www.nature.com/articles/hgv201616

In genetics we have the notion of heritability — how much of a trait is due to genetics, as supposed to environment. For most traits, the amount of heritability we can explain is lower than the estimates of heritability from e.g. twin studies, leading to the notion of “missing heritability” — to be hunted for in NGS data. A new study suggests there may be less missing heritability to be found, because estimates of overall heritability have tended to be inflated, as common elements in environments have not been taken into account: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3618.html

Some standardized terms for clinical reporting of pharmacogenomic variants have been proposed by an international consortium, in the hope that this will help ease PGx data into clinical care. Table : http://www.nature.com/gim/journal/vaop/ncurrent/fig_tab/gim201687t2.html

A review on the promise of re-evaluating WES data over time: http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201688a.html

Market News

Cornell have the first NY State DoH approved somatic exome test. They present their computational framework, and claim that in 82% of cases they found something actionable. They play up their abilities to capture structural variants and recently characterized variants as compared to hotspot panel testing. They have an in house knowledge base for assessing actionability: https://pmkb.weill.cornell.edu/, http://www.nature.com/articles/npjgenmed201619

Software called OncoTrack quantifies the amount of DNA per gene (SPKMG, Sequence Per Kilobase of exon, per Megabase of the mappable Genome), aimed at CNV and LOH analyses. The measure is proposed to be helpful for looking for phenotype associations, and for tracking a cancer over time. It operates on BAM files. http://www.nature.com/articles/srep29647

Pathway Emerge will be using the software of GenomOncology, who have a solution for labs reporting out on molecular tests (NGS, FISH, karyotyping, RT-PCR, IHC, and others): https://www.genomeweb.com/informatics/pathline-emerge-begins-using-genomoncology-molecular-testing-workflow

Sanford Medicine will be using Translational Medicine’s software for reporting, initial focus on pharmacogenomics: https://www.genomeweb.com/informatics/sanford-health-adds-commercial-pgx-support-personalized-medicine-initiative-expands

N-of-One, who provide curated info on somatic variants, raised a $7m Series B: https://www.genomeweb.com/informatics/n-one-raises-7m-series-b-financing-round

LabCorp are purchasing Sequenom, who produce non-invasive prenatal tests, for $302m. https://www.genomeweb.com/molecular-diagnostics/labcorp-acquire-sequenom-302m-cash.

Phosphorous, a new computational genomics company, has raised $10m Series A. They have a test for predicting cardiac risk, and a test for familial hypercholesterolemia, with plans for more. They aim to be the “hub of a new computational biology network”: https://www.genomeweb.com/molecular-diagnostics/computational-genomics-startup-phosphorus-closes-10m-series-financing-round

Commentary and Context

James Watson is not impressed by the cancer moonshot, calling it “crap”, and “the same old people with the same old ideas”: https://www.statnews.com/2016/07/20/james-watson-cancer/

The ACMG have said non-invasive prenatal screening can replace conventional testing for trisomies 21, 18, and 13 in most women: http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201697a.html

Carl Zimmer is keeping on with his “Game of Genomes”: season 1 here, https://www.statnews.com/feature/game-of-genomes/season-one/, season 2 here, https://www.statnews.com/feature/game-of-genomes/season-two/.

The WSJ on healthy people and genome sequencing, giving pilot results from the PeopleSeq project, investigating healthy human attitudes to genome sequencing, e.g. reasons given. Predictably one of the comments is the one word “GATTACA”: http://www.wsj.com/articles/why-knowing-your-genetic-data-can-be-a-tricky-proposition-1466993160