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Detecting sample swaps in diverse NGS data types using linkage disequilibrium

Nauman Javed, Yossi Farjoun, Tim J. Fennell, Charles B. Epstein, Bradley E. Bernstein, Noam Shoresh
2020 Nature Communications  
As the number of genomics datasets grows rapidly, sample mislabeling has become a high stakes issue. We present CrosscheckFingerprints (Crosscheck), a tool for quantifying sample-relatedness and detecting incorrectly paired sequencing datasets from different donors. Crosscheck outperforms similar methods and is effective even when data are sparse or from different assays. Application of Crosscheck to 8851 ENCODE ChIP-, RNA-, and DNase-seq datasets enabled us to identify and correct dozens of
more » ... labeled samples and ambiguous metadata annotations, representing ~1% of ENCODE datasets.
doi:10.1038/s41467-020-17453-5 pmid:32728101 fatcat:hi7hm4eijnerpiueap5ayz2bbi

Recombination dynamics of clusters in intense extreme-ultraviolet and near-infrared fields

Bernd Schütte, Tim Oelze, Maria Krikunova, Mathias Arbeiter, Thomas Fennel, Marc J J Vrakking, Arnaud Rouzée
2015 New Journal of Physics  
We investigate electron-ion recombination processes in clusters exposed to intense extremeultraviolet (XUV) or near-infrared (NIR) pulses. Using the technique of reionization of excited atoms from recombination (REAR), recently introduced in Schütte et al (2014 Phys. Rev. Lett. 112 253401), a large population of excited atoms, which are formed in the nanoplasma during cluster expansion, is identified under both ionization conditions. For intense XUV ionization of clusters, we find that the
more » ... ficance of recombination increases for increasing cluster sizes. In addition, larger fragments are strongly affected by recombination as well, as shown for the case of dimers. We demonstrate that for mixed Ar-Xe clusters exposed to intense NIR pulses, excited atoms and ions are preferentially formed in the Xe core. As a result of electron-ion recombination, higher charge states of Xe are efficiently suppressed, leading to an overall reduced expansion speed of the cluster core in comparison to the shell.
doi:10.1088/1367-2630/17/3/033043 fatcat:37uaqkgrxvf6pcac73mcbtwsqu

Peripherally Selective Diphenyl Purine Antagonist of the CB1 Receptor

Alan Fulp, Katherine Bortoff, Yanan Zhang, Rodney Snyder, Tim Fennell, Julie A. Marusich, Jenny L. Wiley, Herbert Seltzman, Rangan Maitra
2013 Journal of Medicinal Chemistry  
Antagonists of the CB1 receptor can be useful in the treatment of several important disorders. However, to date, the only clinically approved CB1 receptor antagonist, rimonabant, was withdrawn because of adverse central nervous system (CNS)-related side effects. Since rimonabant's withdrawal, several groups are pursuing peripherally selective CB1 antagonists. These compounds are expected to be devoid of undesirable CNS-related effects but maintain efficacy through antagonism of peripherally
more » ... essed CB1 receptors. Reported here are our latest results toward the development of a peripherally selective analog of the diphenyl purine CB1 antagonist otenabant 1. Compound 9 (N-{1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]piperidin-4-yl}pentanamide) is a potent, orally absorbed antagonist of the CB1 receptor that is >50-fold selective for CB1 over CB2, highly selective for the periphery in a rodent model, and without efficacy in a series of in vivo assays designed to evaluate its ability to mitigate the central effects of Δ(9)-tetrahydrocannabinol through the CB1 receptor.
doi:10.1021/jm401129n pmid:24041123 pmcid:PMC4281022 fatcat:44jrv7pujnfrjppk2mpsi6ush4

ContEst: estimating cross-contamination of human samples in next-generation sequencing data

Kristian Cibulskis, Aaron McKenna, Tim Fennell, Eric Banks, Mark DePristo, Gad Getz
2011 Computer applications in the biosciences : CABIOS  
Here, we present ContEst, a tool for estimating the level of cross-individual contamination in next generation sequencing data. We demonstrate the accuracy of ContEst across a range of contamination levels, sources, and read depths using sequencing data mixed in-silico at known concentrations. We applied our tool to published cancer sequencing data sets and report their estimated contamination levels. Availability and Implementation: ContEst is a GATK (McKenna, et al., 2010) module, and distributed under a BSD style license at
doi:10.1093/bioinformatics/btr446 pmid:21803805 pmcid:PMC3167057 fatcat:uyflbid2pzhrlievlcomxe7np4

Adjusting Choice Models to Better Predict Market Behavior

Greg Allenby, Geraldine Fennell, Joel Huber, Thomas Eagle, Tim Gilbride, Dan Horsky, Jaehwan Kim, Peter Lenk, Rich Johnson, Elie Ofek, Bryan Orme, Thomas Otter (+1 others)
2005 Marketing letters  
, 1988 Fennell, , 1997 .  ...  domain-specific motivating conditions prospects face in the context of their lives, for which they seek product attributes and benefits, generate brands to consider, and select brands to buy and use (see Fennell  ... 
doi:10.1007/s11002-005-5885-1 fatcat:go5l5rstrfbvhcrx22bjq7uauy

Effect of Src kinase inhibition on metastasis and tumor angiogenesis in human pancreatic cancer

Ivan Ischenko, Markus Guba, Maksim Yezhelyev, Armine Papyan, Gerald Schmid, Tim Green, Michael Fennell, Karl-Walter Jauch, Christiane J. Bruns
2007 Angiogenesis  
doi:10.1007/s10456-007-9071-3 pmid:17486419 fatcat:quas4z7fzzgrlporcew4rwrycm

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

Ian Woolhouse, Lesley Bishop, Liz Darlison, Duneesha De Fonseka, Anthony Edey, John Edwards, Corinne Faivre-Finn, Dean A Fennell, Steve Holmes, Keith M Kerr, Apostolos Nakas, Tim Peel (+5 others)
2018 Thorax  
Dr Tim Peel i4 Woolhouse I, et al. Thorax 2018;73:i1-i30. doi:10.1136/thoraxjnl-2017-211321 BTS guideline represented the Association for Palliative Medicine.  ...  Professor Dean Fennell and Dr Jeremy Steel represented the Association of Cancer Physicians. Dr Anthony Edey represented the British Society of Thoracic Imaging.  ... 
doi:10.1136/thoraxjnl-2017-211321 pmid:29444986 fatcat:ltjod2wcnbhgdiihl6yltfrqje

Scaling accurate genetic variant discovery to tens of thousands of samples [article]

Ryan Poplin, Valentin Ruano-Rubio, Mark A. DePristo, Tim J. Fennell, Mauricio O. Carneiro, Geraldine A. Van der Auwera, David E. Kling, Laura D. Gauthier, Ami Levy-Moonshine, David Roazen, Khalid Shakir, Joel Thibault (+8 others)
2017 bioRxiv   pre-print
Comprehensive disease gene discovery in both common and rare diseases will require the efficient and accurate detection of all classes of genetic variation across tens to hundreds of thousands of human samples. We describe here a novel assembly-based approach to variant calling, the GATK HaplotypeCaller (HC) and Reference Confidence Model (RCM), that determines genotype likelihoods independently per-sample but performs joint calling across all samples within a project simultaneously. We show by
more » ... calling over 90,000 samples from the Exome Aggregation Consortium (ExAC) that, in contrast to other algorithms, the HC-RCM scales efficiently to very large sample sizes without loss in accuracy; and that the accuracy of indel variant calling is superior in comparison to other algorithms. More importantly, the HC-RCM produces a fully squared-off matrix of genotypes across all samples at every genomic position being investigated. The HC- RCM is a novel, scalable, assembly-based algorithm with abundant applications for population genetics and clinical studies.
doi:10.1101/201178 fatcat:etmy2npc25h3ljcbinqjrakmhm

BTS guideline for the investigation and management of malignant pleural mesothelioma

Ian Woolhouse, Lesley Bishop, Liz Darlison, Duneesha de Fonseka, Anthony Edey, John Edwards, Corinne Faivre-Finn, Dean A Fennell, Steve Holmes, Keith M Kerr, Apostolos Nakas, Tim Peel (+5 others)
2018 BMJ Open Respiratory Research  
The full guideline for the investigation and management of malignant pleural mesothelioma is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.
doi:10.1136/bmjresp-2017-000266 pmid:29531746 pmcid:PMC5844375 fatcat:czxyv7szxzcaxag7hb5e7f2pzu

Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

Tim P. Green, Mike Fennell, Robin Whittaker, Jon Curwen, Vivien Jacobs, Jack Allen, Armelle Logie, Judith Hargreaves, D. Mark Hickinson, Robert W. Wilkinson, Paul Elvin, Brigitte Boyer (+8 others)
2009 Molecular Oncology  
Src Preclinical Invasion Biomarkers Saracatinib A B S T R A C T AZD0530, an orally available Src inhibitor, demonstrated potent antimigratory and antiinvasive effects in vitro, and inhibited metastasis in a murine model of bladder cancer. Antiproliferative activity of AZD0530 in vitro varied between cell lines (IC 50 0.2 -> 10 mM). AZD0530 inhibited tumor growth in 4/10 xenograft models tested and dynamically inhibited in vivo phosphorylation of Src substrates paxillin and FAK in both
more » ... ibition-resistant and -sensitive xenografts. The activity of AZD0530 in NBT-II bladder cancer cells in vitro was consistent with inhibition of cell migration and stabilization of cell-cell adhesion. These data suggest a dominant anti-invasive pharmacology for AZD0530 that may limit tumor progression in a range of cancers. AZD0530 is currently in Phase II clinical trials.
doi:10.1016/j.molonc.2009.01.002 pmid:19393585 pmcid:PMC5527863 fatcat:j5rdh62bsjc4bd5hmwqznyr3ti

Recombination-Enhanced Surface Expansion of Clusters in Intense Soft X-Ray Laser Pulses

Daniela Rupp, Leonie Flückiger, Marcus Adolph, Tais Gorkhover, Maria Krikunova, Jan Philippe Müller, Maria Müller, Tim Oelze, Yevheniy Ovcharenko, Benjamin Röben, Mario Sauppe, Sebastian Schorb (+10 others)
2016 Physical Review Letters  
We studied the nanoplasma formation and explosion dynamics of single large xenon clusters in ultrashort, intense x-ray free-electron laser pulses via ion spectroscopy. The simultaneous measurement of single-shot diffraction images enabled a single-cluster analysis that is free from any averaging over the cluster size and laser intensity distributions. The measured charge state-resolved ion energy spectra show narrow distributions with peak positions that scale linearly with final ion charge
more » ... e. These two distinct signatures are attributed to highly efficient recombination that eventually leads to the dominant formation of neutral atoms in the cluster. The measured mean ion energies exceed the value expected without recombination by more than an order of magnitude, indicating that the energy release resulting from electron-ion recombination constitutes a previously unnoticed nanoplasma heating process. This conclusion is supported by results from semiclassical molecular dynamics simulations.
doi:10.1103/physrevlett.117.153401 pmid:27768378 fatcat:arlkqwpy3jg6xebqijzkrkvlaq

A framework for variation discovery and genotyping using next-generation DNA sequencing data

Mark A DePristo, Eric Banks, Ryan Poplin, Kiran V Garimella, Jared R Maguire, Christopher Hartl, Anthony A Philippakis, Guillermo del Angel, Manuel A Rivas, Matt Hanna, Aaron McKenna, Tim J Fennell (+6 others)
2011 Nature Genetics  
Recent advances in sequencing technology make it possible to comprehensively catalog genetic variation in population samples, creating a foundation for understanding human disease, ancestry and evolution. The amounts of raw data produced are prodigious, and many computational steps are required to translate this output into high-quality variant calls. We present a unified analytic framework to discover and genotype variation among multiple samples simultaneously that achieves sensitive and
more » ... fic results across five sequencing technologies and three distinct, canonical experimental designs. Our process includes (i) initial read mapping; (ii) local realignment around indels; (iii) base quality score recalibration; (iv) SNP discovery and genotyping to find all potential variants; and (v) machine learning to separate true segregating variation from machine artifacts common to next-generation sequencing technologies. We here discuss the application of these tools, instantiated in the Genome Analysis Toolkit, to deep whole-genome, whole-exome capture and multi-sample low-pass (~4×) 1000 Genomes Project datasets.
doi:10.1038/ng.806 pmid:21478889 pmcid:PMC3083463 fatcat:sndpnklmjvcq5eololmluztt4u

Exome Sequencing,ANGPTL3Mutations, and Familial Combined Hypolipidemia

Kiran Musunuru, James P. Pirruccello, Ron Do, Gina M. Peloso, Candace Guiducci, Carrie Sougnez, Kiran V. Garimella, Sheila Fisher, Justin Abreu, Andrew J. Barry, Tim Fennell, Eric Banks (+15 others)
2010 New England Journal of Medicine  
doi:10.1056/nejmoa1002926 pmid:20942659 pmcid:PMC3008575 fatcat:uhav576gdzglfejbn6e6an7o2y

The experimental design and data interpretation in 'Unexpected mutations after CRISPR Cas9 editing in vivo' by Schaefer et al. are insufficient to support the conclusions drawn by the authors [article]

Christopher J. Wilson, Tim Fennell, Anne Bothmer, Morgan L. Maeder, Deepak Reyon, Cecilia Cotta-Ramusino, Cecilia A. Fernandez, Eugenio Marco, Luis A. Barrera, Hariharan Jayaram, Charles F. Albright, Gerald F. Cox (+2 others)
2017 bioRxiv   pre-print
The recent correspondence to the Editor of Nature Methods by Schaefer et. al. has garnered significant attention since its publication as a result of its strong conclusions contradicting numerous publications in the field using similar analytical approaches and methods. The authors suggest that the CRISPR-Cas9 system is highly mutagenic in genomic regions not expected to be targeted by the gRNA. Based on experimental design and a re-analysis of the primary data, we believe that the conclusions
more » ... rawn from this study are unsubstantiated by the disclosed experiments as they were designed and carried out. Further, it is impossible to ascribe the observed differences in the subject mice to the effects of CRISPR per se. The genetic differences seen in this comparative analysis were likely present prior to editing with CRISPR.
doi:10.1101/153338 fatcat:jep67d2sond7jjet6sjkraqmim

A polygenic burden of rare disruptive mutations in schizophrenia

Shaun M. Purcell, Jennifer L. Moran, Menachem Fromer, Douglas Ruderfer, Nadia Solovieff, Panos Roussos, Colm O'Dushlaine, Kimberly Chambert, Sarah E. Bergen, Anna Kähler, Laramie Duncan, Eli Stahl (+20 others)
2014 Nature  
doi:10.1038/nature12975 pmid:24463508 pmcid:PMC4136494 fatcat:547gn4c5lvhmfbgoz3ikl2regu
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