‘Jumping genes’ drive many cancers

‘Jumping genes’ drive many cancers

Mistakes in DNA are known to drive cancer growth. But a new study, from Washington University School of Medicine in St. Louis, heavily implicates a genetic phenomenon commonly known as “jumping genes” in the growth of tumors.

The study is published March 29 in the journal Nature Genetics.

Since jumping genes aren’t mutations — mistakes in the letters of the DNA sequence — they can’t be identified by traditional cancer genome sequencing. As such, this study opens up new lines of research for future cancer therapies that might target such genes.

Jumping genes, which scientists call transposable elements, are short sections of the DNA sequence that have been incorporated randomly into the genome over the long course of human evolution. The evolutionary histories of jumping genes are the subject of much current research, but viral infection is thought to play an important role in their origins.

Researchers led by Ting Wang, PhD, the Sanford C. and Karen P. Loewentheil Distinguished Professor of Medicine, have plumbed genomic databases, looking specifically for tumors whose jumping genes are driving cancer growth.

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Canopy Biosciences aims to capitalize on Sequencing Error-Correction

Canopy Biosciences Aims to Improve Rare Variant Detection With Error-Correction Sequencing Service

NEW YORK (GenomeWeb) – After receiving an exclusive license from the Washington University in St. Louis for its error-correction sequencing technology, startup Canopy Biosciences now plans to develop the bioinformatic tool further to identify and monitor ultra-rare gene variants in patient blood samples.

With the new license, Canopy will build upon its gene expression analysis portfolio by offering a streamlined research-use-only service for next-generating sequencing applications.

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Origins and Evolution of Mental Health Genetic Variants

Illumina and the Lundbeck Foundation GeoGenetics Centre Collaborate to Generate One of the Largest Ancient Genome Datasets to Decode the Genetic Origins and Evolution of Mental Health Issues

SAN DIEGO--(BUSINESS WIRE)--Illumina (NASDAQ:ILMN) and the Lundbeck Foundation GeoGenetics Centre at the University of Copenhagen, Denmark partner to explore the relationship between the evolutionary history of select mental and neurological disorders and infectious pathogens. One of the first projects of its kind worldwide, the endeavor aims to acquire new knowledge in terms of the medical and biological understanding of special factors underlying the development of human neuropsychiatric diseases through the ages. Ultimately, the project may provide a new approach to the development of medicines and other therapeutic treatments for mental and neurological conditions.

Where do brain disorders come from? In an effort to shed light on the role of microbes in the pathogenesis of neuropsychiatric illnesses, such as Alzheimer’s disease and schizophrenia, Professor Eske Willerslev and his team will build one of the largest genomic datasets of its kind, by complete DNA mapping of thousands of ancient Eurasian human remains. The data will be obtained from bones and teeth, the oldest remains dating back 10,000 years.

The international, multi-disciplinary team of scientists, which includes specialists in ancient genomics, neuro-genetics, population genetics, archaeology, linguistics, and experts in brain health, among others, will focus on creating two unique subsets of genomic data. The first panel is a 5,000 ancient human genomes panel. The second panel will consist of ancient pathogen DNA that is associated with human diseases. Both panels, which will be made publicly available, will together advance our understanding of the evolution of disease variance and its interaction with the human genome and pathogen pressure. The project will generate and analyze one of the largest sets of ancient human and pathogen genome panels ever created.

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Mapping the pharmacogenomic drug response landscape

Encircling the regions of the pharmacogenomic landscape that determine drug response

Adrià Fernández-Torras, Miquel Duran-Frigola & Patrick Aloy

Genome Medicine (Research Article)

Background

The integration of large-scale drug sensitivity screens and genome-wide experiments is changing the field of pharmacogenomics, revealing molecular determinants of drug response without the need for previous knowledge about drug action. In particular, transcriptional signatures of drug sensitivity may guide drug repositioning, prioritize drug combinations, and point to new therapeutic biomarkers. However, the inherent complexity of transcriptional signatures, with thousands of differentially expressed genes, makes them hard to interpret, thus giving poor mechanistic insights and hampering translation to clinics.

Methods

To simplify drug signatures, we have developed a network-based methodology to identify functionally coherent gene modules. Our strategy starts with the calculation of drug-gene correlations and is followed by a pathway-oriented filtering and a network-diffusion analysis across the interactome.

Results

We apply our approach to 189 drugs tested in 671 cancer cell lines and observe a connection between gene expression levels of the modules and mechanisms of action of the drugs. Further, we characterize multiple aspects of the modules, including their functional categories, tissue-specificity, and prevalence in clinics. Finally, we prove the predictive capability of the modules and demonstrate how they can be used as gene sets in conventional enrichment analyses.

Conclusions

Network biology strategies like module detection are able to digest the outcome of large-scale pharmacogenomic initiatives, thereby contributing to their interpretability and improving the characterization of the drugs screened.

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A high-quality raspberry genome assembly is on its way

BerryWorld Plus wins KeyGene’s genome-for-free contest

KeyGene is pleased to announce that BerryWorld Plus has won the genome-for-free contest, organised on the occasion of the Genome Insights meetup on 21 March 2019 in Wageningen. The raspberry breeders at BerryWorld Plus will receive a high-quality genome assembly of a genotype of their choice.  BerryWorld Plus was selected because they are a leader in considering state-of-the-art technology to accelerate the development of premium, healthy raspberries. With this high-quality genomic resource, raspberry breeding can now fully benefit from KeyGene’s ample experience and state of the art technologies.

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Where mutations are not tolerated: a good summary of an outstanding study

Big datasets pinpoint new regions to explore the genome for disease

A dataset of more than 100,000 individuals allows researchers to identify genetic regions that are intolerant to change and may underlie developmental disorders.

Imagine rain falling on a square of sidewalk. While the raindrops appear to land randomly, over time a patch of sidewalk somehow remains dry. The emerging pattern suggests something special about this region. This analogy is akin to a new method devised by researchers at University of Utah Health. They explored more than 100,000 healthy humans to identify regions of our genes that are intolerant to change. They believe that DNA mutations in these "constrained" regions may cause severe pediatric diseases.

"Instead of focusing on where DNA changes are, we looked for parts of genes where DNA changes are not," said Aaron Quinlan, Ph.D., associate professor of Human Genetics and Biomedical Informatics at U of U Health and associate director of the USTAR Center for Genetic Discovery. "Our model searches for exceptions to the rule of dense genetic variation in this massive dataset to reveal constrained regions of genes that are devoid of variation. We believe these regions may be lethal or cause extreme phenotypes of disease when mutated."

While this approach is conceptually simple, only recently has there been enough human genomes available to make it happen. These new, invariable stretches may reveal new disease-causing genes and can be used to help pinpoint the cause of disease in patients with developmental disorders. The results of this study are available online in the December 10 issue of the journal Nature Genetics.

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Targeting Brain Tumors with Single-Cell RNA-seq

Brain Tumors Through the Single-Cell RNA Sequencing Lens: Researcher Interview with Mario Suvà

Read Peggy Wang’s interview with Mario Suvà for the National Cancer Institute. Dr. Suvà is an assistant professor of pathology at Massachusetts General Hospital and Harvard Medical School, an Institute Member at the Broad Institute, and uses single-cell RNA sequencing as a discovery tool for understanding brain cancer. Lean more about his work and this powerful new approach to understanding this important disease…

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New advance increasing the effectiveness of immunotherapies for cancer treatment

Harnessing T-cell “stemness” could enhance cancer immunotherapy

A new study led by scientists in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI) sheds light on one way tumors may continue to grow despite the presence of cancer-killing immune cells. The findings, published March 29, 2019, in Science, suggest a way to enhance the effectiveness of immunotherapies for cancer treatment. NCI is part of the National Institutes of Health.

Dying cancer cells release the chemical potassium, which can reach high levels in some tumors. The research team reported that elevated potassium causes T cells to maintain a stem-cell-like quality, or “stemness,” that is closely tied to their ability to eliminate cancer during immunotherapy. The findings suggest that increasing T cells’ exposure to potassium—or mimicking the effects of high potassium—could make cancer immunotherapies more effective.

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BRCA Challenge creates database for fighting cancer

BRCA Exchange aggregates data on thousands of BRCA variants to inform understanding of cancer risk

A global resource that includes data on thousands of inherited variants in the BRCA1 and BRCA2 genes is available to the public. The BRCA Exchange was created through the BRCA Challenge, a long-term demonstration project initiated by the Global Alliance for Genomics and Health (GA4GH) to enhance sharing of BRCA1 andBRCA2 data. The resource, available through a website and a new smartphone appExit Disclaimer, allows clinicians to review expert classifications of variants in these major cancer predisposition genes as part of their individual assessment of complex questions related to cancer prevention, screening, and intervention for high-risk patients. 

The five-year BRCA Challenge project was funded in part by the National Cancer Institute (NCI), part of the National Institutes of Health, and through the Cancer Moonshot℠. A paper detailing the development of the BRCA Exchange was published January 8, 2019, in PLOS Genetics. READ MORE …

Promise of cheap and fast CRISPR-based diagnostics

Handheld CRISPR device to enable faster diagnosis of genetic disease

A team of researchers in the US has developed a handheld device that diagnoses genetic diseases at point-of-care. Called CRISPR-Chip, the device combines a deactivated clustered regularly interspaced short palindromic repeats (CRISPR) Cas9 protein with electronic transistors to identify genetic mutations in DNA samples without the need for amplification or replication of the DNA segment using the polymerase chain reaction (PCR).

Avoiding the time-consuming PCR step is expected to enable the use of CRISPR-Chip for genetic testing in a doctor’s office or field work setting, rather than sending samples to a laboratory.

The method can also be used to assess the accuracy of gene-editing techniques.

The researchers included scientists from the University of California, Berkeley (UC Berkeley) and the Keck Graduate Institute (KGI) of The Claremont Colleges.

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And watch the promo video HERE …

Good review of major microbial genome web portals

A Comparison of Microbial Genome Web Portals

Peter D. Karp, Natalia Ivanova, Markus Krummenacker, Nikos Kyrpides, Mario Latendresse, Peter Midford, Wai Kit Ong, Suzanne Paley, & Rekha Seshadri

Frontiers in Microbiology (Research Article)

Microbial genome web portals have a broad range of capabilities that address a number of information-finding and analysis needs for scientists. This article compares the capabilities of the major microbial genome web portals to aid researchers in determining which portal(s) are best suited to their needs. We assessed both the bioinformatics tools and the data content of BioCyc, KEGG, Ensembl Bacteria, KBase, IMG, and PATRIC. For each portal, our assessment compared and tallied the available capabilities. The strengths of BioCyc include its genomic and metabolic tools, multi-search capabilities, table-based analysis tools, regulatory network tools and data, omics data analysis tools, breadth of data content, and large amount of curated data. The strengths of KEGG include its genomic and metabolic tools. The strengths of Ensembl Bacteria include its genomic tools and large number of genomes. The strengths of KBase include its genomic tools and metabolic models. The strengths of IMG include its genomic tools, multi-search capabilities, large number of genomes, table-based analysis tools, and breadth of data content. The strengths of PATRIC include its large number of genomes, table-based analysis tools, metabolic models, and breadth of data content.

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Gene interactions are a potential key to personalized medicine

Gene interactions identified as personalized medicine’s missing link

“The ability to affordably sequence genomes has prompted numerous predictions about the rise of personalised medicine, however so far this has failed to come to pass. But in research published today, scientists have identified gene interactions as the key barrier to this medical revolution taking off.

Personalised medicine, where individuals are prescribed pharmaceuticals based on their own genetic makeup, has been raised as a possibility since the Human Genome Project was completed in 2003. It was thought that as more people had their genomes sequenced scientists would unearth genes responsible for predispositions to specific diseases, which would enable medication to be tailored to individuals.

However, while tens of thousands of people around the world have now had their genomes sequenced, it has not produced the clear genetic interactions initially predicted. And the reason for this is gene interactions: how different genes impact each other in the results and responses they produce.”

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Walnut genome to be sequenced by UC Davis and USDA

Deciphering the Walnut Genome

“In a new study, a team of scientists at the University of California, Davis, and USDA’s Agricultural Research Service (ARS) used a unique approach to sequence the genomes of the English walnut and its wild North American relative by tapping into the capabilities of two state-of-the-art technologies: long-read DNA sequencing and optical genome mapping. The resulting genome sequences are believed to be of the highest quality ever assembled of any woody perennial.”

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Genome sequencing has been getting cheaper, but library preps haven't--until now

IDT lowers genomic barriers with targeted sequencing system

“Itegrated DNA Technologies (IDT) has introduced its rhAmpSeq targeted sequencing system, providing researchers with highly accurate, cost-effective and easy-to-use amplicon sequencing on Illumina next-generation sequencing (NGS) platforms. The rhAmpSeq chemistry enables multiplexing at impressive levels with high on-target rates and uniform coverage, delivering accurate results and accelerating projects. The system has wide-ranging applications, including human disease research and sample tracking and analysis, CRISPR genome editing analysis and agricultural biotechnology.”

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George Smith on what's to gain from looking into the genomes of extinct furry elephants

Decoding a Mammoth with George Church

Join Harvard DNA pioneer George Church and Chris Smith in conversation as they discuss gene cloning, DNA sequencing, decoding the mammoth genome, the risks posed by fossil viruses lurking in extinct genomes, the prospects of xenotransplantation, and safety of gene therapy, and the risks of human CRISPR. The discussion was recorded on March 15th, live in front of a studio audience at the Hello Tomorrow Summit, in Paris, 2019...

Watch the video here …

The Possibility of Computational DNA

Reprogrammable DNA

“Researchers from the California Institute of Technology and Harvard University have shown that it is possible to reprogram a DNA-based computer, Wired reports.

The team, led by Caltech's Erik Winfree, reports in Nature that it developed and validated a set of 355 DNA tiles that they could then reprogram into a range of six-bit algorithms. In particular, the team says it constructed 21 circuits that perform algorithms that copy, sort, elect a leader, and generate random patterns, among other tasks, with an error rate of less than 1 in 3,000. This, they add, suggests "molecular self-assembly could be a reliable algorithmic component within programmable chemical systems.“

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Cell population mapping from bulk single-cell RNA data

Cell composition analysis of bulk genomics using single-cell data

Amit Frishberg, Naama Peshes-Yaloz, Ofir Cohn, Diana Rosentul, Yael Steuerman, Liran Valadarsky, Gal Yankovitz, Michal Mandelboim, Fuad A. Iraqi, Ido Amit, Lior Mayo, Eran Bacharach, & Irit Gat-Viks

Nature Methods (Research Article)

Abstract—Single-cell RNA sequencing (scRNA-seq) is a rich resource of cellular heterogeneity, opening new avenues in the study of complex tissues. We introduce Cell Population Mapping (CPM), a deconvolution algorithm in which reference scRNA-seq profiles are leveraged to infer the composition of cell types and states from bulk transcriptome data (‘scBio’ CRAN R-package). Analysis of individual variations in lungs of influenza-virus-infected mice reveals that the relationship between cell abundance and clinical symptoms is a cell-state-specific property that varies gradually along the continuum of cell-activation states. The gradual change is confirmed in subsequent experiments and is further explained by a mathematical model in which clinical outcomes relate to cell-state dynamics along the activation process. Our results demonstrate the power of CPM in reconstructing the continuous spectrum of cell states within heterogeneous tissues.

Strata Oncology using NGS for advanced cancer

Strata Oncology Launches Expanded StrataNGS for Patients with Advanced Cancer

ANN ARBOR, Mich., March 19, 2019 /PRNewswire/ -- Strata OncologyTM, a leading precision oncology company, today announced the launch of version 3.0 of StrataNGSTM, its pan-cancer assay for solid tumors. The updated 500-gene assay utilizes DNA and RNA from tumor samples to detect all clinically actionable biomarkers — including microsatellite instability (MSI), tumor mutational burden (TMB), and PD-L1 — recommended by leading guidelines, in a single test. Test results are provided in a streamlined report that facilitates rapid, confident interpretation and identification of potential treatment options and clinical trials.

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New CRISPR Diagnostics Firm

Broad, Wyss Institute Researchers Launch CRISPR Dx Firm Sherlock Biosciences

NEW YORK (GenomeWeb) – Engineering biology startup Sherlock Biosciences announced today that it has launched with initial financing of $35 million and licenses to foundational CRISPR and synthetic biology technology from the Broad Institute and Harvard's Office of Technology Development…

Sherlock will use engineering biology tools, including CRISPR and synthetic biology, to develop a new generation of molecular diagnostics that can rapidly deliver accurate results for a vast range of needs in virtually any setting and at low cost, the company said.

The financing includes a $17.5 million non-dilutive grant and an investment from the Open Philanthropy Project, as well as funds from additional undisclosed investors.

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Combination therapy for cancer therapy

Functional Genomics Approach To Identify New Combination Therapies For Cancer Treatment

“In our recent publication in Science Advances, we describe the use of an in vivo-based functional genomics screen to identify genes whose inhibition potentiates a response to anti-PD-1 immunotherapy. Specifically, we define a novel mechanism whereby targeting the collagen receptor, discoidin domain receptor 2 (DDR2), elicits a significantly enhanced response to immune checkpoint blockade with PD-1 inhibitors. Of specific note is the observation this combination is robust across multiple tumor models including melanoma, sarcoma, breast, bladder and colon cancer indicating that DDR2 expression is an important and broadly used mechanism by cancer cells to escape checkpoint blockade therapy“

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