Round-up May 22nd-30th

A study published today showing CRISPR off-target effects knocked CRISPR stocks, despite the fact that the findings were old news. 

The FDA have approved the first therapy based on molecular feature rather than tissue of origin. About 4% of all advanced cancers have the genetic characteristics involved. Merck won the apporval based on an accelerated” process, off the back of a trial of 149 patients.

The Broad have released the latest version of their genome analysis software, GATK, under an open source license. The software, which has 45,000 users, was previously costly for non-academic use.

A meta-analysis of the genetics behind intelligence identifies several genetic loci that collectively explain 4.8% of the variance in intelligence. An editorial in Nature argues that we have historical reasons to fear the field of intelligence studies (history of racism, history of eugenics, fears of biological determinism), but we shouldn’t this hold us back from showing that there is no genetic basis for discrimination”.

When it comes to complex disease, GWAS have historically found relatively common variants of small effect. Larger sample sizes are a way to go, as is using isolated populations in the hope of identifying founder mutations, as this study does to uncover a variant protective against heart disease.

How rare is rare enough for a variant to be possibly causative of disease? This all important cut-off affects how many variants must be considered when evaluating a case. The paper from the ExAC group that lays out a framework for defining this cut-off is finally out, though of course it was up on BioRxiv months ago, and was previously rounded-up here.

Nature reports that police in Xinjiang, China, have been collecting blood samples and are building up DNA sequencing facilities that go beyond what would be needed for regular forensics. There is no clear framework for legal use of the data.

NPR reports on CRISPR use outside the lab. 

Catch-up! April 4th – May 21st

I’ve moved jobs and had a month traveling since my last round-up. An attempt to capture the most significant happenings over the intervening few weeks below, before resuming my regular weekly schedule.
I am now working for Driver, with a mission to cure cancer, so expect to see an increased emphasis on all things somatic.
Having been blocked from reporting health results for a few years, 23andMe are now allowed to report on 10 diseases direct to consumer, with no physician in the loop. The list does not include tests whose results cold affect treatment decisions (e.g. BRCA1/2)
  • the ACMG are opposed
  • those that they’re at higher risk for Alzheimers are over 6 times as likely to purchase long-term care insurance. Individuals are supposed to share such information with their potential insurer (unlike for health insurance), but the industry fears people won’t (New York Times).
  • on the average, individuals do have measurable lifestyle improvements, and 25% credit their genetic results (improvements were not associated with any particular genetic result). This is in contrast to previous studies, which found no improvement
More than two thirds of ~100 oncologists said they would prescribe immunotherapy rather than a targeted molecular therapy, because the shot of a durable response from the former outweighs the fact that resistant genotypes will be positively selected for in the latter. This follows on from a survey reporting 70% of 132 oncologists said genomic testing was below expectations’.
Two studies on 100 non small-cell lung cancer (NSCLC) cancer patients (the TRACERx study):
  • Samples from many regions finds elevated CNV heterogeneity associated with shorter survival (NEJM
  • Using the tumor sequencing results, the team designed an individualized multiplex-PCR test for each patient, and use the results to show they can predict patient responses/outcomes in some cases (Nature). They also find predictors of which patients have more circulating tumor DNA.
MSK have reported that their IMPACT test for cancer patients identifies clinically relevant mutations for 37% of patients. 11% of patients enrolled on a clinical trial as a result of a variant found. They are optimistic about predicting response to immunotherapy boosting these numbers further (Study N=5009, currently about 17,000 patients).
A study of 100,000 cancers has found that tumor mutational burden (TMB) can be assessed accurately from just ~1.1 Mb of sequence, and report recurrent promoter mutations in PMS2 associated to high TMB.
A study in Nature of the whole genomes of different types of melanoma reveals diverse carcinogenic processes across its subtypes, some unrelated to sun exposure, and reports that most cancers had actionable mutations.
Noninvasive prenatal screening (NIPS) started with chromosomal abnormalities (now reccomended for all pregnancies), and has more recently been extended to the smaller scale microdeletions. Now Natera say they are developing a noninvasive prenatal screening test that will cover  de novo mutations in 30 genes, which will cover diseases that collectively cover diseases found in 1 in 600 births. 
Broad researchers introduced Sherlock via a Science paper: it uses Cas13a, a CRISPR associated protein that targets RNA rather than DNA, as part of a very sensitive molecular diagnostic to detect e.g. strains of Zika, with potential point of care applications
Canada passed an anti-genetic discrimination law that went into effect on May 4, which means no-one can be required to have a genetic test or disclose the results of a genetic test, but PM Trudeau is challenging its constitutionality
Experimental evidence of long-lasting (14 generations) epigenetic memory of environmental change in C elegans