Illumina have sued Oxford Nanopore Technologies for patent infringement. This is based on Illumina holding two patents for the use of the MspA pore. ONT have historically used a different pore, but they have perhaps switched to MspA. GenomeWeb report Oxford Nanopore’s CEO Gordon Sanghera saying, “It is gratifying to have the commercial relevance of Oxford Nanopore products so publicly acknowledged by the market monopolist for NGS.”. All this in the context of ONT soon to have their IPO, and old industry hands pointing out that Illumina launched a patent suit against Complete Genomics just before their IPO.  https://www.genomeweb.com/sequencing-technology/update-illumina-sues-oxford-nanopore-patent-infringement. Additional commentary on the unfolding drama: http://www.opiniomics.org/shots-fired-nanopore-wars-part-ii/.

Paper calling for the end of race in genetics http://science.sciencemag.org/content/351/6273/564, and a useful summary: http://www.newsworks.org/index.php/local/the-pulse/91075-scientists-call-for-the-removal-of-race-in-genetics-research- . “We believe the use of biological concepts of race in human genetic research—so disputed and so mired in confusion—is problematic at best and harmful at worst. It is time for biologists to find a better way.” One better way suggested is the use of the term “ancestry”.

Ultimately, many people born with severe genetic disease have excellent lives. So how much effort should we go to eliminate them? A very interesting read: http://www.nature.com/news/should-you-edit-your-children-s-genes-1.19432.

Robert Califf has been confirmed as the new head of the FDA, https://www.genomeweb.com/scan/califf-confirmed. He wants the FDA to be more proactive in removing bad products from the market.

Highly accurate Muscular Dystrophy diagnoses off of Ion Torrent sequencing: http://www.nature.com/jhg/journal/vaop/ncurrent/full/jhg20167a.html

For NGS data, methods that aggregate variation over genes in order to pick up on associations from case-control studies (e.g. VAAST) are all the rage. These are supplanting the variant-by-variant analyses that dominated the SNP chip world. Burden tests can be followed by procedures to identify actual causal variants (e.g. remove a variant if excluding this variant can lead to a smaller P-value for the gene). Another approach is to continue to score each variant separately, but test for association using “adaptive combination of P-values (ADA)” to pinpoint causal variants: http://www.nature.com/articles/srep21824

Grow sperm in a dish, from stem cells: http://www.sciencemag.org/news/2016/02/new-method-grows-sperm-dish. Post male world, anyone?

 

News from the AGBT Conference, Feb 10th – Feb 13th

• Note this is the first year that they’ve separated Research and Tech (just happened) and Clinical Applications (to be held in September)
• 10X unveiled new pipeline (machine plus application platforms), Chromium, full release due in May. Reminder: synthetic long-reads sequencing can do some things, like long-range phasing, well. Chromium can do Phase blocks which average >10MB, and requires similar coverage to standard Ilumina runs. Phased reads enables much better calling of copy number regions and large indels. They’ve also made good progress towards the first diploid de novo assemblies. Cost for whole genome is $450 on top of $1000. Press release on co-marketing with Ilumina (“10 X on X Ten”): http://www.illumina.com/company/news-center/press-releases/press-release-details.html?newsid=2137067&linkId=21145087.Press release on their new shiny exome: http://www.10xgenomics.com/news/agilent-technologies-and-10x-genomics-announce-collaboration-to-develop-a-premium-exome/
• Nanostring, a no library prep or amplification sequencing technology, still far from commercialization: http://core-genomics.blogspot.com/2016/02/agbt16-day-4-new-sequencing-chemistry.html
• Foundation Medicine released details of their circulating tumor DNA (ctDNA) assay: https://www.genomeweb.com/sequencing-technology/foundation-medicine-describes-ctdna-assay-validation-agbt
• The 100K Genome Asia project was announced, first aim is to make reference genomes for each of the major Asian ethnic groups: http://www.prnewswire.com/news-releases/genomeasia-100k-initiative-announced-to-sequence-100000-genomes-in-south-north-and-east-asia-568523301.html. Note:  Macrogen are involved
• Some details of NASA’s twins study (one in space, one earth bound), which I’m mentioning just because I’d never heard of it, and its cool: http://www.nasa.gov/mission_pages/station/research/experiments/2108.html

 

Research and Reviews

• On Clinical Utility. The ACMG believes that diagnoses, and corresponding changes in disease management, should be sufficient demonstration of clinical utility — even in the absence of evidence for improved clinical outcomes (http://www.nature.com/gim/journal/vaop/ncurrent/full/gim2015153a.html). Payors disagree, e.g. see this lawsuit of a genetic testing company taking a payor to court for not covering their test: https://www.genomeweb.com/molecular-diagnostics/exact-v-humana-lawsuit-reflects-genetic-testing-firms-deepening-adversarial. This week the Office of Public Health Genomics published a position http://www.nature.com/gim/journal/vaop/ncurrent/full/gim2015153a.html, which is a good short read on the complexities of what “clinical utility” means, ultimately arguing for something that is highly context specific.
• On testing of minors. Current ASHG guidelines say there should be no predictive genetic testing of minors (http://www.ncbi.nlm.nih.gov/pubmed/26140447). This short piece outlines the opposing view, http://www.nature.com/gim/journal/vaop/ncurrent/full/gim2015191a.html, drawing on a study just published concerning lack of adverse effects of such testing.
• So, we know that all non-African humans have Neanderthal DNA. But the picture of which other homonoid species we interbred with, and how, just got a whole lot more complicated: http://www.sciencemag.org/news/2016/02/humans-mated-neandertals-much-earlier-and-more-frequently-thought
• Some of the genetic basis of musical ability uncovered: http://www.nature.com/articles/srep21198— highlighting many genes (including novel ones) that make sense, e.g. involved in inner ear development, cognition, memory, auditory processing, and genes known to be related to bird song in birds. I find this interesting as a glimpse at a possible future — something not disease related (musical aptitude, other types of ability…), but just as amenable to genetic burden report as a disease area.
• A competitor to algorithms that use phenotype to rank variants, OMIMGeneExplorer: http://www.ncbi.nlm.nih.gov/pubmed/26838676. It incorporates “a simple interface for translating free-text clinical notes into HPO terms”
• Heidi Rehm et al on strategies for Academic Medical Centers: http://www.mdpi.com/2075-4426/6/1/8/htm. In a nutshell: forge commercial partnerships; try and consolidate onto one genomics based test for rare diseases; look to support research projects.
• A review of the current state of the art of single-cell sequencing: http://www.nature.com/nrg/journal/v17/n3/full/nrg.2015.16.html
• PheWas are the younger sibling of the better known GWAS. In Genome Wide Association Studies, you start with cases and controls and find genetic variation that segregates. In a Phenome Wide Association Study, you use phenotype data from EHRs to explore the phenomic consequences of particular genetic variants. PheWAS can be more powerful if you have rich phenotype data. Review of current state of the art: http://www.nature.com/nrg/journal/v17/n3/full/nrg.2015.36.html.
• A study using 23andMe data to look at penetrance (the often missing piece of the puzzle), in this case of prion disease. Write-up here: http://www.nature.com/nrg/journal/v17/n3/full/nrg.2016.9.html. The authors of the paper are a husband and wife team, who got into this research when they found out she had a prion disease, with no current treatment, that will kill her at age 50ish, unless there are major breakthroughs shortly. Read their story here: http://www.bostonglobe.com/magazine/2016/02/17/husband-and-wife-race-cure-her-fatal-genetic-disease/
• 49% of Americans believe in human evolution, but 75% of Americans believe in elephant evolution http://www.sciencemag.org/news/2016/02/americans-knowledge-evolution-isn-t-bad-if-you-ask-them-about-elephants

Market News

• Sure Genomics — who launched a whole genome, more or less direct to consumer product earlier this month —  had been planning to get around FDA regs: “Sure Genomics loops in a physician from its network to gather information about your family history and order the sequencing that intends to answer your specific questions about your health. The physician then prescribes the sequencing, meaning they technically have oversight of the information you’re about to get back.” There’s also a genetic counsellor involved in the return of results: http://www.businessinsider.com/sure-genomics-genomic-sequencing-test-2016-2.But they just received an FDA letter saying: “If you do not believe that you are required to obtain FDA clearance for the SureDNA test, please provide us with the basis of that determination.”
• Sophia Genetics (variant calling, annotation,algorithms, reporting, http://www.sophiagenetics.com/hospitals/sophia-ddm/sophia-ddmtm-details.html) partner with Swift Biosciences (sequencing), aiming to capture European market: https://www.genomeweb.com/informatics/sophia-genetics-partners-swift-biosciences-offer-mdx-solution
• LabCorp are doing well, largely thanks to their Covance acquisition: https://www.genomeweb.com/molecular-diagnostics/boosted-covance-acquisition-labcorp-posts-48-percent-revenue-growth-q4
• Genomics England announced partnerships with
  • Icon, for data management: https://www.genomeweb.com/informatics/genomics-england-taps-icon-manage-100k-genomic-data
  • Ilumina, for genome interpretation https://www.genomeweb.com/business-news/illumina-genomics-england-partner-improve-genomic-interpretation. This was not an expected announcement.

• Invitae is selling far more tests than last year, but lost $90m in 2015. This year they will introduce a panel aimed at healthy individuals: https://www.genomeweb.com/molecular-diagnostics/invitaes-q4-revenues-increase-more-threefold
• Seven Bridges, who do bioinformatics in the cloud for genomics, have raised $45m. That will go on head count, especially in their new SF office: https://www.genomeweb.com/informatics/seven-bridges-genomics-raises-45-million-series
• Military personnel (active and veteran) can now get a genetic test designed to look at mental health genetics (“pharmacogenetic test for psychiatry”) for free: https://genomind.com/news/genetic-testing-for-mental-health-approved-as-new-ally-for-military-personnel-and-veterans/

 

23andMe links being a morning person and genetics. The GWAS type analysis found 15 regions, several near known circadian rhythm genes. http://www.nature.com/ncomms/2016/160202/ncomms10448/full/ncomms10448.html

Oxford Nanopore’s MinION has been at work, producing “real time, portable sequencing for Ebola surveillance”: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature16996.html Using the MinION (which weighs less than 100g), “We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15–60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.”

Last February, the UK approved the creation of three person embryos, where the mitochondria came from a third donor. The FDA had requested an Institute of Medicine report on the technique. Published this week, the report concluded with various caveats that it could be ethical — but limited to male embryos for the moment (males do not pass on mitochondria, so the changes made would affect only the individual in question). http://www.nap.edu/catalog/21871/mitochondrial-replacement-techniques-ethical-social-and-policy-considerations. However, the latest federal budget “prevents the FDA from using funds to review applications in which a human embryo is intentionally created or modified to include” changes that could be passed down to future generations.

A link between genes near an individual’s disrupted transcription factor binding sites and their phenotype data is established in this paper, in a further foray beyond the exome: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004711. This mutational load/burden style approach used data from five individuals who have made both their whole genomes and medical histories public.

Common disease: the product of many common variants, or a few rare ones? GWAS, which only look at common variants, have not been able to explain much genetic predisposition. This study looked at both common and rare variants for AMD http://www.ncbi.nlm.nih.gov/pubmed/26691988: “Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.” Also see a writeup at MassGenomics http://massgenomics.org/2016/02/rare-variant-studies-of-common-disease.html.

Two reasons senescent cells (those that no longer undergo cell division) have been in the news.

• They have been shown to have different chromosome structure http://www.sciencedaily.com/releases/2016/02/160205144509.htm.
• Getting rid of senescent cells in mice helps extend “healthspan”, in a large step forward in aging research  http://www.theatlantic.com/science/archive/2016/02/clearing-retired-cells-extends-life/459723/

 

In a follow on to the case of the child who was forced to leave a Palo Alto school because he was a CF carrier, the U.S. Departments of Education and Justice have filed a brief siding with the family and against Palo Alto school district, arguing that the decision violoated both his first ammendament prviacy rights and the Americans with Disabilities Act http://www.paloaltoonline.com/news/2016/02/08/feds-weigh-in-on-palo-alto-dna-privacy-case

A Nature Editorial draws attention to how hard it is to get a paper corrected or retracted, even if it is clearly wrong, and even by the authors of the study: http://www.nature.com/news/reproducibility-a-tragedy-of-errors-1.19264