Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.

Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics

Crisis opportunism: bailouts and E-SCADs in the GFC

As a response to the junk debt-inspired global economic crisis, governments, with supra-national organizational approval, have appropriated billions of taxpayers dollars for bailouts, have set up special funds and underwritten depositors savings in the desperate hope of alleviating the threat of rapid, economic decline and systemic destruction of value. Whether these governments have a democratic mandate for such unprecedented action is debatable. More importantly, though, is whether such decisions amount to good re-regulatory policy. First, it is known that some of the bailout money to large corporations has been squandered by oligarchic recipients and appropriated by them in their own interests. Second, special funds, set up supposedly to support particular industry sectors from liquidation, have been attacked on the basis that they have only served to support crony capitalism and attract oligarchic rent-seeking writ large. Third, Australian banks, for example, which have government, depositor account guarantees have made windfall gains. The worst-case scenario is that governments have used taxpayers funds with a flagrant disregard for the consequences, including abusing inter-generational utility, and have actually committed economic, state crimes. Public policy in Neo-liberalism is fraught with crisis vulnerability. Crises, as created opportunities, compound the situation. From US congressional earmarks, to Yankee and Met owners scams siphoning billions in public funds, policy discourse around the world has been high-jacked by opportunistic Neo-liberalism. This article seeks to deconstruct some of the hubris associated with corporate capitalism\u27s creation of a new financial sector based on fraud - junk debt, credit default swaps and derivatives. How has it come to pass that fraud has become the basis of corporate performance and leadership remuneration? Is criminal fraud the heart of global capitalism and a criminogenic Neo-liberalism? This article explores these issues, qualitatively, through a forensic examination of emerging re-regulatory policies in the United States and Australia. The conceptual framework of the article is located within the notion of economic, state crimes against democracy