DASC-PM v1.0 : ein Vorgehensmodell für Data-Science-Projekte

Das Thema Data Science hat in den letzten Jahren in vielen Organisationen stark an Aufmerksamkeit gewonnen. Häufig herrscht jedoch weiterhin große Unklarheit darüber, wie diese Disziplin von anderen abzugrenzen ist, welche Besonderheiten der Ablauf eines Data-Science-Projekts besitzt und welche Kompetenzen vorhanden sein müssen, um ein solches Projekt durchzuführen. In der Hoffnung, einen kleinen Beitrag zur Beseitigung dieser Unklarheiten leisten zu können, haben wir von April 2019 bis Februar 2020 in einer offenen und virtuellen Arbeitsgruppe mit Vertretern aus Theorie und Praxis das vorliegende Dokument erarbeitet, in dem ein Vorgehensmodell für Data-Science-Projekte beschrieben wird – das Data Science Process Model (DASC-PM). Ziel war es dabei nicht, neue Herangehensweisen zu entwickeln, sondern viel-mehr, vorhandenes Wissen zusammenzutragen und in geeigneter Form zu strukturieren. Die Ausarbeitung ist als Zusammenführung der Erfahrung sämtlicher Teilnehmerinnen und Teilnehmer dieser Arbeitsgruppe zu verstehen

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.This study was funded by the UK Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1. This work was supported by the MRC Metabolic Diseases Unit (MC_UU_12012/5) and the Cambridge NIHR Biomedical Research Centre and EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant 115372). Funding for the InterAct project was provided by the EU FP6 program (grant LSHM_CT_2006_037197). This work was funded, in part, through an EFSD Rising Star award to R.A.S. supported by Novo Nordisk. D.B.S. is supported by Wellcome Trust grant 107064. M.I.M. is a Wellcome Trust Senior Investigator and is supported by the following grants from the Wellcome Trust: 090532 and 098381. M.v.d.B. is supported by a Novo Nordisk postdoctoral fellowship run in partnership with the University of Oxford. I.B. is supported by Wellcome Trust grant WT098051. S.O'R. acknowledges funding from the Wellcome Trust (Wellcome Trust Senior Investigator Award 095515/Z/11/Z and Wellcome Trust Strategic Award 100574/Z/12/Z)

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

3DCeraTurb: Design and manufacture of CMC stator guide vanes for high-pressure turbines

Increasing the performance and efficiency of aero engines is essential for more environmentally friendly air transport. Rising temperatures, especially for combustion section and turbine structures, as well as lower weight of the components are key requirements for new materials. Together with adapted environmental coating systems and cooling features, ceramic composites are good candidates for aircraft applications. They are capable of withstanding high temperatures in an aggressive environment, while the density is two-thirds lower than conventional nickel-based alloys. As part of the DLR project “3DCeraTurb”, the Institute of Structures and Design and the Institute of Materials Research, along with several other DLR institutes, are developing turbine guide vanes made of silicon carbide fibre-reinforced silicon carbide composites (SiC/SiC CMC) and all-oxide CMC, respectively. One aim of 3DCeraTurb is to design and manufacture ceramic stator guide vanes for a high-pressure turbine, to experimentally investigate the vane behaviour in a wind tunnel and to evaluate performance, damage and lifetime for later application in an aircraft engine. The focus is the enhancement of the respective manufacturing processes from plate dimensions to more complex three-dimensional components. A ceramic-based design is the basis for the development and manufacture of a new guide vane geometry, taking into consideration material- and manufacturing-specific constraints. The manufacturing and development processes of the SiC/SiC and oxide CMC components will be presented with a particular focus on SiC/SiC. The SiC/SiC fabrication starts with the draping and CVI fibre coating of woven fabrics, followed by resin infiltration via resin transfer moulding. The final steps involve pyrolysis and liquid silicon infiltration. Surface grinding and laser drilling of cooling holes in the trailing edge are challenging parts during the final machining of the vanes. CFD simulations connected to FEM simulations are carried out accompanying the design and manufacturing process. The safety factors for the wind tunnel and the cruise load case are calculated using the Tsai-Wu criterion

A modular device for large area integrated photoelectrochemical water-splitting as a versatile tool to evaluate photoabsorbers and catalysts

We present a stand-alone integrated solar water-splitting module with an active area of 64 cm2 and a long-term stable operation. As a photocathode we employ multijunction thin film silicon solar cells that were optimized to deliver a suitable output voltage for spontaneous water-splitting. Two approaches for the design of a suitable front contact are presented to reduce series resistance losses related to the upscale of the photoelectrodes. The photoelectrode is protected from the electrolyte by a sheet metal which connects the rear contact of the solar cell with the hydrogen evolving catalyst. Thereby, the sheet metal ensures long-term stability while the electrical and thermal coupling of the solar cell and the electrolysis cell is maintained. Due to the modular setup, which allows us to vary and optimize the device components (i.e. the solar cell, catalysts, membrane, and electrolyte) individually, the presented water-splitting device provides a convenient toolbox for the optimization of such systems

Mutations of the CHEK2 gene in patients with cancer and their presence in the Latin American population

Artículo científicoCHEK2 (Checkpoint Kinase 2) encodes CHK2, a serine/threonine kinase involved in maintaining the G1/S and G2/M checkpoints and repair of double-strand DNA breaks via homologous recombination. Functions of CHK2 include the prevention of damaged cells from going through the cell cycle or proliferating and the maintenance of chromosomal stability. CHEK2 mutations have been reported in a variety of cancers including glioblastoma, ovarian, prostate, colorectal, gastric, thyroid, and lung cancer in studies performed mainly in White populations. The most studied mutation in CHEK2 is c.1100delC, which was associated with increased risk of breast cancer. The objective of this study was to compile mutations in CHEK2 identified in cancer genomics studies in different populations and especially in Latin American individualsIntroduction. -- Search of cancer genomics data repositories and the GWAS catalog. -- Literature review of Latin American studies. -- Results. -- CHEK2 mutations in the data genomics repositories. -- CHEK2 mutations in Latinos reported in the literature. -- Discussion