UK Research and Innovation awards £45 million to EMBL’s European Bioinformatics Institute (EMBL-EBI)

Funding awarded for bioinformatics infrastructure

UK Research and Innovation (UKRI) has awarded £45 million to EMBL’s European Bioinformatics Institute (EMBL-EBI), to enhance the institute’s technical and building infrastructure. The funding, which comes from the UKRI’s Strategic Priorities Fund, will support EMBL-EBI’s existing and emerging data resources, including in areas of major interest, such as genomics and bioimaging.

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Minimap2 makes sophisticated analysis possible on hand-held devices

The Garvan Institute brings DNA analysis capabilities to smartphones

The Garvan Institute of Medical Research has partnered with the University of NSW to take genome analysis ‘offline’ by adapting the algorithms that perform DNA analysis to require far less compute than current tools.

Minimap2 makes sophisticated analysis possible on hand-held devices. Genome Media.

Medical practitioners fighting the Ebola and Zika viruses in New Guinea and Brazil have already used small genome sequencing devices that can clip on to a smartphone, but these devices still require high-performance computer workstations or reliable internet connections to identify genes.

Devices like the Oxford Nanopore Technologies MinION can create over a terabyte of data in 48 hours, but their use still isn’t commonplace because comparing or ‘aligning’ DNA from an unknown sample to a reference database to figure out what the sample is requires around 16 GB of RAM, which is beyond the capabilities of most mid-range laptops and flagship smartphones.

For cash-strapped medical programs in developing countries or during large-scale outbreaks, that kind of processing power isn’t easy to come by at scale, and a reliable internet connection can be just as hard to find.

In a new paper released in Nature, Garvan’s Genomic Technologies lead Dr Martin Smith and his team detailed the computational method for reducing the amount of memory needed for aligning sequences from 11GB to 2GB - well within the reach of mid-range smartphones.

The researchers adapted the Minimap2 program, which aligns DNA sequencing ‘reads’ to a reference library of known genomes.


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We'll need AI to deal with coming wave of genome data

Getting smart about artificial intelligence

By: Alison Cranage, Science writer

We'll need AI to deal with coming wave of genome data. Genome Media.

“Genomics is set to become the biggest source of data on the planet, overtaking the current leading heavyweights – astronomy, YouTube and Twitter. Genome sequencing currently produces a staggering 25 petabytes of digital information per year. A petabyte is 1015 bytes, or about 1,000 times the average storage on a personal computer. And there is no sign of a slowdown.”


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Moratorium on heritable genome editing covered by MIT Technology Review

CRISPR experts are calling for a global moratorium on heritable gene editing

After the first International Summit on Human Gene Editing in December 2015, a statement was released. The organizers were unanimous in agreeing that the creation of genetically modified children was “irresponsible” unless we knew for sure it was safe.

Well, a fat lot of good that did. As MIT Technology Review revealed in November last year, Chinese scientist He Jiankui edited embryos to create two genetically engineered babies. Other groups are now actively looking to use the technology to enhance humans.

This has prompted some of the biggest names in gene editing (some of whom signed the 2015 statement) to call for a global moratorium on all human germline editing—editing sperm or egg cells so that the changes are hereditary.

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Also, we suggest reading the whole Rewriting Life series at the MIT Technology Review.

Conflict over proposed heritable genome editing moratorium covered in Science

New call to ban gene-edited babies divides biologists

John Cohen sums up the conflict nicely in Science

Conflict over proposed heritable genome editing moratorium covered in Science. Genome Media.

A prominent group of 18 scientists and bioethicists from seven countries has called for a global “moratorium” on introducing heritable changes into human sperm, eggs, or embryos—germline editing—to make genetically altered children. The group, which published a commentary in Naturetoday, hopes to influence a long-standing debate that dramatically intensified after China’s He Jiankui announced in November 2018 that he used the genome editor CRISPR to try to alter the genes of babies to be resistant to the AIDS virus.

Their call, which is endorsed in the same issue of Nature by Francis Collins, director of the U.S. National Institutes of Health, is a departure from statements issued by two global summits on genome editing in 2015 and 2018, a 2017 report from the U.S. National Academies of Sciences, Engineering, and Medicine (NASEM), and a 2018 report from the United Kingdom’s Nuffield Council on Bioethics. None has banned human germline editing, and most have stressed that it holds promise to help correct some heritable diseases. All have warned against using germline editing for cognitive or physical “enhancement” of people. Scientists including Nobel laureate David Baltimore of the California Institute of Technology in Pasadena remain opposed to a moratorium. Even in the wake of the He incident, Baltimore, who helped organize the summits, denounced such a ban as “draconian” and “antithetical to the goals of science.”


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National Academies on the Call for Moratorium on and International Governance of Heritable Gene Editing

Statement on Call for Moratorium on and International Governance Framework for Clinical Uses of Heritable Genome Editing

“A commentary published in Nature calls for a moratorium on clinical uses of heritable human genome editing and the establishment of an international governance framework. (We responded to the commentary with a joint letter, which is an abbreviated version of this statement.) The call comes following claims by a scientist in China to have edited the genes of early embryos, in treatments that resulted in the birth of twins. The scientist’s work – revealed at the Second International Summit on Human Genome Editing in Hong Kong, jointly organized by our Academies, was condemned by the summit organizers and by much of the wider scientific community.”

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Heavyweights call for moratorium on heritable genome editing

Adopt a moratorium on heritable genome editing

Eric Lander, Françoise Baylis, Feng Zhang, Emmanuelle Charpentier, Paul Berg and specialists from seven countries call for an international governance framework.

Heavyweights call for moratorium on heritable genome editing. Genome Media.

We call for a global moratorium on all clinical uses of human germline editing — that is, changing heritable DNA (in sperm, eggs or embryos) to make genetically modified children.

By ‘global moratorium’, we do not mean a permanent ban. Rather, we call for the establishment of an international framework in which nations, while retaining the right to make their own decisions, voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met.


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A boozy view of the human genome project, where it's been and might go

Human Genome Project: new alcohol abuse study could help us finally unlock secrets to beating genetic diseases

A boozy view of the human genome project, where it's been and might go. Genome Media

“Geneticists tried to exploit the revelations about the genome with studiesthat combed through thousands of tiny genetic changes in hundreds of thousands of patients with different diseases to see how they compared to healthy people. This enabled them to correlate genetic changes in diseased DNA in a manner unimaginable before June 2000. The “genetic architecture” of a wide number of conditions from cancers to schizophrenia to addiction became much better understood as a result.

Yet after the first few thousand studies were published, geneticists were horrified to discover that 98% of the disease-associated changes they’d identified in the genome do not occur in the genes. Instead, the vast majority of changes related to disease occur in the 98% of the genome that is not made up of genes – known as the “junk genome”, since few had the foggiest notion of what it was or how to study it.”


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Gencove expanding whole genome sequencing

Gencove raises $3M investment led by Spero Ventures to expand genome sequencing platform

Gencove expanding whole genome sequencing. Genome Media

NEW YORK, /PRNewswire/ -- Gencove, the leading low-pass genome sequencing platform, announced today a $3 million investment led by Spero Ventures. Alexandria Venture Investments and Burst Capital participated in the round, along with existing investors Third Kind Venture Capital and Version One Ventures. The funding will be used to develop new applications for agricultural markets as well as expand Gencove's commercial operations in human genetics. Shripriya Mahesh, partner at Spero, will join Gencove's board of directors.

"Genomics will be foundational to the health and well-being of humanity and the planet," said Shripriya Mahesh. "We are excited partner with Gencove in its mission to bring affordable whole genome sequencing to customers and industries that have never before been able to affordably integrate it at scale."


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Positive results for Epic prostate cancer testing

Blood Test Study Meets Goal, Validates Epic’s Prostate Cancer Target

Positive results for Epic prostate cancer testing. Genome Media.

Epic Sciences has commercialized a blood test that can predict how likely a patient with late-stage prostate cancer treated with hormones is likely to respond to an additional course of such therapy. Now, the San Diego-based company has additional data that it says supports use of its tests to determine when not to use hormone therapy



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Insights into the bugs in your guts, their diversity and associations with disease

Novel insights from uncultivated genomes of the global human gut microbiome

Insights into the bugs in your guts, their diversity and associations with disease. Genome Media

“Largely due to challenges cultivating microbes under laboratory conditions, the genome sequence of many species in the human gut microbiome remains unknown. To address this problem, we reconstructed 60,664 prokaryotic draft genomes from 3,810 faecal metagenomes from geographically and phenotypically diverse human subjects. These genomes provide reference points for 2,058 previously unknown species-level operational taxonomic units (OTUs), representing a 50% increase in the phylogenetic diversity of sequenced gut bacteria. On average, new OTUs comprise 33% of richness and 28% of species abundance per individual and are enriched in humans from rural populations. A meta-analysis of clinical gut microbiome studies pinpointed numerous disease associations for new OTUs, which have the potential to improve predictive models. Finally, our analysis revealed that uncultured gut species have undergone genome reduction with loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.”


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Gene expression used for leukemia diagnostics

Gene expression patterns identify high-risk chronic lymphocytic leukemia

Gene expression used for leukemia diagnostics. Genome Media.

A 290-gene expression signature and IGHV mutation status stratified patients with chronic lymphocytic leukemia to identify those with high-risk disease who might benefit from prompt initiation of therapy, according to a study published in Frontiers in Oncology.

Although CLL treatment is typically delayed until disease progression, it is uncertain whether patients would benefit from treatment immediately following diagnosis, when they have a smaller tumor mass and are in better physical condition.


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Berkeley gets another CRISPR patent

University of California granted another CRISPR patent

UC Berkeley announced Tuesday it received a patent for a single-molecule guide RNA that can be used with the Cas-9 enzyme by the gene-editing tool CRISPR in plants, bacteria and mammalian cells.

Why it matters: Discovering new methods of making CRISPR's gene editing more precise are key to its future success in modifying crops and treating diseases. But, there's also a race among institutions — especially between UC and the Broad Institute — to own CRISPR patents that are potentially worth billions, per Reuters.

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Background: CRISPR can use different enzymes, most often Cas9, to target specific genes for editing, but there remain safety concerns, as it's been shown to sometimes cause unwanted deletions, edit the wrong genes or move genes around. Guide RNAs can be used to locate the proper DNA sequence that needs to be cut.

By the numbers: This is UC Berkeley's third CRISPR patent and they expect a fourth to be issued soon.

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or go even deeper: UC Berkeley team awarded second CRISPR-Cas9 patent

The origins of an important cancer causing virus

Origin and evolution of papillomavirus (onco)genes and genomes

Anouk Willemsen and Ignacio G. Bravo

biorxiv (Research Article)

Abstract—Papillomaviruses (PVs) are ancient viruses infecting vertebrates, from fish to mammals. Although the genomes of PVs are small and show conserved synteny, PVs display large genotypic diversity and ample variation in the phenotypic presentation of the infection. Most PVs genomes contain two small early genes E6 and E7. In a bunch of closely related human PVs, the E6 and E7 proteins provide the viruses with oncogenic potential. The recent discoveries of PVs without E6 and E7 in different fish species place a new root on the PV tree, and suggest that the ancestral PV consisted of the minimal PV backbone E1-E2-L2-L1. Bayesian phylogenetic analyses date the most recent common ancestor of the PV backbone to 424 million years ago (Ma). Common ancestry tests on extant E6 and E7 genes indicate that they share respectively a common ancestor dating back to at least 184 Ma. In AlphaPVs infecting primates, the appearance of the E5 oncogene 53-58 Ma concurred with i) a significant increase in substitution rate, ii) a basal radiation, and iii) key gain of functions in E6 and E7. This series of events was instrumental to build the extant phenotype of oncogenic human PVs. Our results assemble the current knowledge on PV diversity and present an ancient evolutionary timeline punctuated by evolutionary innovations in the history of this successful viral family.

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Viral coinfection increases variation, fitness

Beneficial coinfection can promote within-host viral diversity 

Asher Leeks, Ernesto A. Segredo-Otero, Rafael Sanjuán, and Stuart A. West

Virus Evolution (Research Article)

Viral coinfection increases variation, fitness. Genome Media.

Abstract—In many viral infections, a large number of different genetic variants can coexist within a host, leading to more virulent infections that are better able to evolve antiviral resistance and adapt to new hosts. But how is this diversity maintained? Why do faster-growing variants not outcompete slower-growing variants, and erode this diversity? One hypothesis is if there are mutually beneficial interactions between variants, with host cells infected by multiple different viral genomes producing more, or more effective, virions. We modelled this hypothesis with both mathematical models and simulations, and found that moderate levels of beneficial coinfection can maintain high levels of coexistence, even when coinfection is relatively rare, and when there are significant fitness differences between competing variants. Rare variants are more likely to be coinfecting with a different variant, and hence beneficial coinfection increases the relative fitness of rare variants through negative frequency dependence, and maintains diversity. We further find that coexisting variants sometimes reach unequal frequencies, depending on the extent to which different variants benefit from coinfection, and the ratio of variants which leads to the most productive infected cells. These factors could help drive the evolution of defective interfering particles, and help to explain why the different segments of multipartite viruses persist at different equilibrium frequencies.


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Paradigm-shifting discovery in virology--multicellular replication!

A multicellular way of life for a multipartite virus

Anne Sicard, Elodie Pirolles, Romain Gallet, Marie-Stéphanie Vernerey, Michel Yvon, Cica Urbino, Michel Peterschmitt, Serafin Gutierrez, Yannis Michalakis, and Stéphane Blanc

eLife (Research Article)

Abstract

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A founding paradigm in virology is that the spatial unit of the viral replication cycle is an individual cell. Multipartite viruses have a segmented genome where each segment is encapsidated separately. In this situation the viral genome is not recapitulated in a single virus particle but in the viral population. How multipartite viruses manage to efficiently infect individual cells with all segments, thus with the whole genome information, is a long-standing but perhaps deceptive mystery. By localizing and quantifying the genome segments of a nanovirus in host plant tissues we show that they rarely co-occur within individual cells. We further demonstrate that distinct segments accumulate independently in different cells and that the viral system is functional through complementation across cells. Our observation deviates from the classical conceptual framework in virology and opens an alternative possibility (at least for nanoviruses) where the infection can operate at a level above the individual cell level, defining a viral multicellular way of life.

Lucence improving personalized liver cancer treatment with AI

Lucence Diagnostics to Develop AI Tools for Liver Cancer Treatment

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Lucence Diagnostics, a genomic medicine company focused on personalizing cancer care, today announced a new project to develop AI algorithms for improving diagnosis and treatment of liver cancer. The goal is to combine the imaging and molecular data from liver cancer patients into smarter software tools that help physicians make better treatment decisions.

Lucence will be working with Olivier Gevaert, PhD, Assistant Professor of Medicine (Biomedical Informatics) and of Biomedical Data Science at the Stanford University School of Medicine. Having developed LiquidHALLMARK®, the world's first liquid biopsy next-generation sequencing test that analyzes the DNA of cancer-causing mutations and viruses, Lucence will contribute its genomics expertise and proprietary sequencing technology to this project.


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Coverage of the Genome-wide Off-target analysis by Two-cell embryo Injection

A Tool To Validate The Safety Of Gene Editing Systems

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AsianScientist (Mar. 12, 2019) – A team of international scientists has developed a technique to evaluate the safety of genome-editing techniques. The research was published in Science. CRISPR-Cas9 is a new generation of gene-editing tool that has been widely used. However, the risk of off-target effects in vivo, which could lead to diseases such as cancer, remains a serious concern. A variety of off-target detection schemes have been developed, with most relying on the prediction of off-target sites based on sequence similarity or in vitro amplification. However, the latter process may introduce a large amount of noise, thus making it difficult to separate off-target signals from background noise. Whether CRISPR-Cas9 induces off-target effects has been controversial.



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Read the original article at Science

Insights into how cancers escape an important class of treatments

Genome-wide screening identifies novel genes and biological processes implicated in cisplatin resistance

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Abstract

Cisplatin-based chemotherapeutic regimens are frequently used for treatments of solid tumors. However, tumor cells may have inherent or acquired cisplatin resistance, and the underlying mechanisms are largely unknown. We performed genome-wide screening of genes implicated in cisplatin resistance in A375 human melanoma cells. A substantial fraction of genes whose disruptions cause cisplatin sensitivity or resistance overlap with those whose disruptions lead to increased or decreased cell growth, respectively. Protein translation, mitochondrial respiratory chain complex assembly, signal recognition particle–dependent cotranslational protein targeting to membrane, and mRNA catabolic processes are the top biologic processes responsible for cisplatin sensitivity. In contrast, proteasome-mediated ubiquitin-dependent protein catabolic process, negative regulations of cellular catabolic process, and regulation of cellular protein localization are the top biologic processes responsible for cisplatin resistance. ZNRF3, a ubiquitin ligase known to be a target and negative feedback regulator of Wnt–β-catenin signaling, enhances cisplatin resistance in normal and melanoma cells independently of β-catenin. Ariadne-1 homolog (ARIH1), another ubiquitin ligase, also enhances cisplatin resistance in normal and melanoma cells. By regulating ARIH1, neurofibromin 2, a tumor suppressor, enhances cisplatin resistance in melanoma but not normal cells. Our results shed new lights on cisplatin resistance mechanisms and may be useful for development of cisplatin-related treatment strategies.—Ko, T., Li, S. Genome-wide screening identifies novel genes and biological processes implicated in cisplatin resistance.


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Epigenetics: Fascinating but under appreciated sources and effects (original article)

Biological Invasion: The Influence of the Hidden Side of the (Epi)Genome

Abstract

bee-invasion.jpg

1.Understanding the mechanisms underlying biological invasions and rapid adaptation to global change remains a fundamental challenge, particularly in small populations lacking in genetic variation. Two under‐studied mechanisms that could facilitate adaptive evolution and adaptive plasticity are the increased genetic variation due to transposable elements, and associated or independent modification of gene expression through epigenetic changes.

2.Here we focus on the potential role of these genetic and non‐genetic mechanisms for facilitating invasion success. Because novel or stressful environments are known to induce both epigenetic changes and transposable element activity, these mechanisms may play an underappreciated role in generating phenotypic and genetic variation for selection to act on. We review how these mechanisms operate, the evidence for how they respond to novel or stressful environments, and how these mechanisms can contribute to the success of biological invasions by facilitating adaptive evolution and phenotypic plasticity.

3.Because genetic and phenotypic variations due to transposable elements and epigenetic changes are often well regulated or “hidden” in the native environment, the independent and combined contribution of these mechanisms may only become important when populations colonize novel environments. A focus on the mechanisms that generate and control the expression of this variation in new environments may provide insights into biological invasions that would otherwise not be obvious.

4.Global changes and human activities impact on ecosystems and allow new opportunities for biological invasions. Invasive species succeed by adapting rapidly to new environments. The degree to which rapid responses to environmental change could be mediated by the epigenome – the regulatory system that integrates how environmental and genomic variation jointly shape phenotypic variation ‐ requires greater attention if we want to understand the mechanisms by which populations successfully colonize and adapt to new environments.


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