What a week. On Tuesday, a report a year in the making said that germline genome modification should not be prohibited — an update on the previous position that it would be irresponsible to proceed without broad societal consensus. The story was picked up just about everywhere. I’ve been thinking about it for a couple of days, and have summarized my disagreement with the report here.

Then on Wednesday the CRISPR patent dispute went in favor of the Broad/MIT/Harvard rather than UC Berkeley/University of Vienna. The latter group were the first to show use of CRISPR as a genome editing technique in bacteria, and filed patents covering all cell types. But the Boston set were the first to show that it also worked in eukaryotic cells, and filed for this use. The California group claimed that these patents overlapped with their own, but the Patent Trial and Appeal Board judged that the Boston patents did not interfere: “because one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in an eukaryotic environment”. Editas, which has an exclusive license to medical breakthroughs resulting from the patents in dispute, saw its stock jump by more than 30% on the news. Summaries from the Broad and from UC, the latter stating they are “pleased that its patent application covering the use of CRISPR-Cas9 gene editing technology for all cell types can now move closer to issuance”. That is, this is not over yet.

In other gene therapy related news, researchers have successfully made a mouse glow after injecting it with the mRNA of the same protein that makes fireflies glow. This type of gene therapy would be transient, and particularly suitable for vaccinations — current vaccines involve introducing viral material in order to get the bodies immune system to respond; this technology could potentially directly instruct the body to produce its own antigens. The key to the work was the development of a molecule that helps get mRNAs into cells.

High overall tumor mutational burden (TMB) is an indicator for response to immunotherapy, probably because more mutations means more neoantigens, means more targets for the immune system in combating the cancer. PGDx are developing a circulating tumor DNA test, targeted at regions in the genome that their previous exome sequencing work has indicated are good surrogates for overall TMB.

The move to pre-prints in biology is heating up, with ASAPBio launching its plan to become a centralized repository. The twittersphere reacted strongly, saying that we already have that with the bioRxiv.

There are dozens of genetic changes that have an impact on presence of genetic diseases. A group in Michigan published something that they think many of them have in common: they fall in regions where the transcription factor “Regulatory Factor X” is predicted to bind in islets, groups of cells in the pancreas that produce insulin.

In an article entitled “The next pseudoscience health craze is all about genetics“, Gizmodo argues, using very specific advice given out by DNA Lifestyle Coach as an example, that “lifestyle advice has a tendency to sound more like it was divined from a health-conscious oracle than from actual science”.

For clinical adoption of genetic tests, health providers want to see evidence it works. Startup Geneticure are launching an 800 person prospective randomized controlled trial of their pharmacogenomics test for hypertension drugs, hoping to show that their test enables patients to get to controlled blood pressure faster, with less medication.

Okay, this isn’t actually from this week, but I missed it, and its worth rounding-up. In October those involved in the Genome write project launched a white paper. “The Genome Project-write (GP-write) will use synthesis and genome editing technologies to understand, engineer and test living systems.” Its main goal is to drive technology development, and particularly to lower the cost of writing genomes. A sub goal is to “understand the functional properties and phenotypic consequences” of the human genome. Possible pilot projects mentioned include:

• Making cancer resistant human organs in vitro
• Making human cell lines able to produce vitamins and all amino acids (which humans, unlike some bacteria, have not evolved the ability to do)
• Transforming the pig genome to make it “far more amenable” for human organ transplantation
• Making an “ultrasafe” human cell line (its worth checking out what properties they’re aiming for on p14, includes virus resistant, radiation resistant, cancer resistant, to name but a few)

They want to launch the project with over $100m pledged, and have a tentative roadmap. A proportion of funding should go to ethical, social and legal issues raised: “We encourage public discourse to occur surrounding HGP-write, and that having these conversations well in advance of deliverables will help society better prepare for and guide emerging capabilities.”

A  paper, summarized with implications by GenomeWeb, illustrates just how widespread the problem of DNA damage is, induced for example by library prep. They find evidence for DNA Damage in the 1000 genomes data, for example. They come up with a score to quantify the amount of damage in a sample. A computational approach can be taken to reduce the effect of these errors: “One way to deal with damaged-induced sequencing errors is to filter out affected reads, which can be flagged because the G to T mutations occur only in one read direction but not the other.”

A great success story from the Cincinnati Children’s Cancer and Blood Diseases Institute, who report on the successful use of sequencing for patients with histiocytic disorders, with impacted clinical outcomes.

In other research news: The Oxford MinION is sensitive enough to pick up methylation patterns; Coffee consumption is associated with DNA methylation levels of human blood; evidence that “Untimely expression of gametogenic genes” can cause uniparental disomy (UPD) — UPD in humans usually leads tocongenital disease; some replicated, exome wide significant associations to bipolar disorder, including rare coding variants for the first time; genetics of self-reported tiredness.