Round-up, Jan 10th – 26th

(I know this covers more than one week… not off to a good start!)

Jan 11th-14th was the JPMorgan conference, with several announcements coming from the annual gathering of biotech top brass. 

Ilumina announced Grail, a product that will attempt to detect early stage cancer from blood. Isn’t this stepping on their customers’ toes? Their CEO Flatley on this point: “In this case, we didn’t think the market could do it fast enough, unless we destroyed our [business] by giving away sequencing. We don’t think anyone else can do it at scale. And there are millions of lives at stake.” The project will involve Clinical trails of >30,000 people; $100m investment; test available 2019.

Just a few days later, Obama announced his “cancer moonshot” (and was careful to avoid the word ‘cure’): Biden is in charge of “mission control”.

I thought this was interesting to hear from Myriad (from JPMorgan): “Capone also reiterated that 80 percent of samples the firm receives for hereditary cancer testing are now orders for its myRisk Hereditary Cancer panel, a 25-gene, next-gen sequencing-based test. And despite competitors entering the market, he said the firm hasn’t seen a lot of price erosion, which he attributed to Myriad’s lab accuracy, variant classification database, and customer support”.

And while still on the subject of cancer, NCI-Match is a basket trail for precision medicine cancer therapies: you send in your sample, it assigns you to a trial based on the variants. Its been very popular, but had spectacularly low matching rates to date. Genomeweb’s piece is an interesting read: Comparison point to current start of the art: “At Mass General, where doctors routinely perform next-generation sequencing on metastatic cancer patients and have access to an extensive portfolio of studies that they could potentially place patients in, more than 40 percent of patients receive actionable results.” 

DNASimple, a Y combinator startup, is growing a database of DNA donors (rare disease, other), who they will ask for saliva samples if a research project needs them.

We’ve seen quite a lot of high-throughput experimental approaches to determine effect of unseen variants (e.g. this early study on missense variants in BRCA1: Here’s a company that is doing similar things to build up a database aimed at “eliminating variants of unknown significance”:

And my picks of interesting science:

CRSIPR-Cas9 was used in child and adult mice models of Muscular Dystrophy to restore dystrophin function, the protein that is needed for normal muscular function, with promising results — bringing gene editing cures much closer:

A review of non-coding variants in cancer. Table 1 gives a nice summary of non-coding annotation source — ENCODE the clear leader, but plenty of others:

In good news for interpreting non-coding regions, high-throughput use of CRISPR-Cas9 to investigate effect of variation on regulatory regions.

More links reported between CNVs and autism

New sequencing technologies to keep an eye on: scientists at NIST are developing a graphene based “hybrid solid-state and biological nanopore”.

A randomized, controlled trial to see if it is a good idea to disclose secondary findings to patients concludes “yes”:

Here’s a study that investigates over 4000 genes are only expressed on one chromosome (relevant for interpreting a heterozygous loss of function variant), which reports that these genes are subject to a lot of intra-human variation — you often see high frequency variants in these genes.

Finally, do we have ten times as many bacterial cells as human cells in our bodies? No, the ratio is more like 1:1.


Genomics: what’s in a name?

Genome, derived from Gene, traces its roots via Pangen to Darwin’s controversial notion of Pangenesis.

Darwin’s decades of research on the inheritance of characteristics had left open an important question. What was the mechanism of inheritance? In 1868, nearly ten years after the publication of The Origin of Species, he framed a hypothesis, which he termed Pangenesis, from the Greek pan (a prefix meaning “whole”, “encompassing”) and genesis (“birth”). He hypothesized the existence of particles, named gemmules, which were shed by every part of the body before coming together in the sperm or egg. It allowed for the possibility of the inheritance of acquired characteristics, and was never that popular.

In 1889 a Dutch botanist called Hugo de Vries proposed his own theory of the inheritance of characteristics, also based on hypothesized particles. He called these pangenes, later shortened to genes.

But what was a gene? Biochemists had been studying the molecules on which life is based, including the cellular components termed chromosomes. In 1910, an American scientist, Thomas Hunt Morgan, was pioneering a new field of study at the intersection of genetics and biochemistry, now known as molecular biology. He was able to show, via a series of experiments on fruit flies, that genes resided on chromosomes. Genes had suddenly become physical. The term genome, introduced in 1920, is a fusion of gene and chromosome, and means the totality of an organism’s genetic material.

In 1987, a group of molecular biologists that were studying the structure, function and evolution of genomes, proposed the term genomics as the title of a new journal. The “-omics” suffix has come to imply the systematic, large-scale, data-driven study of a given domain.

It seems very fitting to have a name that incorporates three essential aspects of the field: inherited information, its physical manifestation, and methodology.