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Atul Butte

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https://www.readbyqxmd.com/read/29602903/the-atacama-skeleton
#1
Garry Nolan, Atul Butte
The recent publication of the genetic analysis of the so-called Atacama skeleton [1] has raised important questions in the biological, archaeological, and anthropological communities. We have clearly stated previously that this skeleton should be repatriated and accorded proper respect as human remains, and echo recent demands for its repatriation.
March 30, 2018: Genome Research
https://www.readbyqxmd.com/read/29567674/whole-genome-sequencing-of-atacama-skeleton-shows-novel-mutations-linked-with-dysplasia
#2
Sanchita Bhattacharya, Jian Li, Alexandra Sockell, Matthew J Kan, Felice A Bava, Shann-Ching Chen, María C Ávila-Arcos, Xuhuai Ji, Emery Smith, Narges B Asadi, Ralph S Lachman, Hugo Y K Lam, Carlos D Bustamante, Atul J Butte, Garry P Nolan
Over a decade ago, the Atacama humanoid skeleton (Ata) was discovered in the Atacama region of Chile. The Ata specimen carried a strange phenotype-6-in stature, fewer than expected ribs, elongated cranium, and accelerated bone age-leading to speculation that this was a preserved nonhuman primate, human fetus harboring genetic mutations, or even an extraterrestrial. We previously reported that it was human by DNA analysis with an estimated bone age of about 6-8 yr at the time of demise. To determine the possible genetic drivers of the observed morphology, DNA from the specimen was subjected to whole-genome sequencing using the Illumina HiSeq platform with an average 11...
March 22, 2018: Genome Research
https://www.readbyqxmd.com/read/29485622/immport-toward-repurposing-of-open-access-immunological-assay-data-for-translational-and-clinical-research
#3
Sanchita Bhattacharya, Patrick Dunn, Cristel G Thomas, Barry Smith, Henry Schaefer, Jieming Chen, Zicheng Hu, Kelly A Zalocusky, Ravi D Shankar, Shai S Shen-Orr, Elizabeth Thomson, Jeffrey Wiser, Atul J Butte
Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components-Private Data, Shared Data, Data Analysis, and Resources-for data archiving, dissemination, analyses, and reuse...
February 27, 2018: Scientific Data
https://www.readbyqxmd.com/read/29351777/are-minor-alleles-more-likely-to-be-risk-alleles
#4
Takashi Kido, Weronika Sikora-Wohlfeld, Minae Kawashima, Shinichi Kikuchi, Naoyuki Kamatani, Anil Patwardhan, Richard Chen, Marina Sirota, Keiichi Kodama, Dexter Hadley, Atul J Butte
BACKGROUND: Genome-wide association studies (GWASs) have revealed relationships between over 57,000 genetic variants and diseases. However, unlike Mendelian diseases, complex diseases arise from the interplay of multiple genetic and environmental factors. Natural selection has led to a high tendency of risk alleles to be enriched in minor alleles in Mendelian diseases. Therefore, an allele that was previously advantageous or neutral may later become harmful, making it a risk allele. METHODS: Using data in the NHGRI-EBI Catalog and the VARIMED database, we investigated whether (1) GWASs more easily detect risk alleles and (2) facilitate evolutionary insights by comparing risk allele frequencies of different diseases...
January 19, 2018: BMC Medical Genomics
https://www.readbyqxmd.com/read/29317701/a-genome-wide-association-study-identifies-only-two-ancestry-specific-variants-associated-with-spontaneous-preterm-birth
#5
Nadav Rappoport, Jonathan Toung, Dexter Hadley, Ronald J Wong, Kazumichi Fujioka, Jason Reuter, Charles W Abbott, Sam Oh, Donglei Hu, Celeste Eng, Scott Huntsman, Dale L Bodian, John E Niederhuber, Xiumei Hong, Ge Zhang, Weronika Sikora-Wohfeld, Christopher R Gignoux, Hui Wang, John Oehlert, Laura L Jelliffe-Pawlowski, Jeffrey B Gould, Gary L Darmstadt, Xiaobin Wang, Carlos D Bustamante, Michael P Snyder, Elad Ziv, Nikolaos A Patsopoulos, Louis J Muglia, Esteban Burchard, Gary M Shaw, Hugh M O'Brodovich, David K Stevenson, Atul J Butte, Marina Sirota
Preterm birth (PTB), or the delivery prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. Although twin studies estimate that maternal genetic contributions account for approximately 30% of the incidence of PTB, and other studies reported fetal gene polymorphism association, to date no consistent associations have been identified. In this study, we performed the largest reported genome-wide association study analysis on 1,349 cases of PTB and 12,595 ancestry-matched controls from the focusing on genomic fetal signals...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29208398/future-cancer-research-priorities-in-the-usa-a-lancet-oncology-commission
#6
REVIEW
Elizabeth M Jaffee, Chi Van Dang, David B Agus, Brian M Alexander, Kenneth C Anderson, Alan Ashworth, Anna D Barker, Roshan Bastani, Sangeeta Bhatia, Jeffrey A Bluestone, Otis Brawley, Atul J Butte, Daniel G Coit, Nancy E Davidson, Mark Davis, Ronald A DePinho, Robert B Diasio, Giulio Draetta, A Lindsay Frazier, Andrew Futreal, Sam S Gambhir, Patricia A Ganz, Levi Garraway, Stanton Gerson, Sumit Gupta, James Heath, Ruth I Hoffman, Cliff Hudis, Chanita Hughes-Halbert, Ramy Ibrahim, Hossein Jadvar, Brian Kavanagh, Rick Kittles, Quynh-Thu Le, Scott M Lippman, David Mankoff, Elaine R Mardis, Deborah K Mayer, Kelly McMasters, Neal J Meropol, Beverly Mitchell, Peter Naredi, Dean Ornish, Timothy M Pawlik, Jeffrey Peppercorn, Martin G Pomper, Derek Raghavan, Christine Ritchie, Sally W Schwarz, Richard Sullivan, Richard Wahl, Jedd D Wolchok, Sandra L Wong, Alfred Yung
We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment...
November 2017: Lancet Oncology
https://www.readbyqxmd.com/read/29173314/risky-business-meeting-the-structural-needs-of-transdisciplinary-science
#7
Paul H Wise, Gary M Shaw, Maurice L Druzin, Gary L Darmstadt, Cecele Quaintance, Elina Mäkinen, David A Relman, Stephen R Quake, Atul J Butte, Martin S Angst, Louis J Muglia, George Macones, Deborah Driscoll, Carole Ober, Joe Leigh Simpson, Michael Katz, Jennifer Howse, David K Stevenson
No abstract text is available yet for this article.
December 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29141660/xcell-digitally-portraying-the-tissue-cellular-heterogeneity-landscape
#8
Dvir Aran, Zicheng Hu, Atul J Butte
Tissues are complex milieus consisting of numerous cell types. Several recent methods have attempted to enumerate cell subsets from transcriptomes. However, the available methods have used limited sources for training and give only a partial portrayal of the full cellular landscape. Here we present xCell, a novel gene signature-based method, and use it to infer 64 immune and stromal cell types. We harmonized 1822 pure human cell type transcriptomes from various sources and employed a curve fitting approach for linear comparison of cell types and introduced a novel spillover compensation technique for separating them...
November 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/29106398/asprosin-is-a-centrally-acting-orexigenic-hormone
#9
Clemens Duerrschmid, Yanlin He, Chunmei Wang, Chia Li, Juan C Bournat, Chase Romere, Pradip K Saha, Mark E Lee, Kevin J Phillips, Mahim Jain, Peilin Jia, Zhongming Zhao, Monica Farias, Qi Wu, Dianna M Milewicz, V Reid Sutton, David D Moore, Nancy F Butte, Michael J Krashes, Yong Xu, Atul R Chopra
Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin...
December 2017: Nature Medicine
https://www.readbyqxmd.com/read/29093271/combined-inhibition-of-atypical-pkc-and-histone-deacetylase-1-is-cooperative-in-basal-cell-carcinoma-treatment
#10
Amar N Mirza, Micah A Fry, Nicole M Urman, Scott X Atwood, Jon Roffey, Gregory R Ott, Bin Chen, Alex Lee, Alexander S Brown, Sumaira Z Aasi, Tyler Hollmig, Mark A Ator, Bruce D Dorsey, Bruce R Ruggeri, Craig A Zificsak, Marina Sirota, Jean Y Tang, Atul Butte, Ervin Epstein, Kavita Y Sarin, Anthony E Oro
Advanced basal cell carcinomas (BCCs) circumvent Smoothened (SMO) inhibition by activating GLI transcription factors to sustain the high levels of Hedgehog (HH) signaling required for their survival. Unfortunately, there is a lack of efficacious therapies. We performed a gene expression-based drug repositioning screen in silico and identified the FDA-approved histone deacetylase (HDAC) inhibitor, vorinostat, as a top therapeutic candidate. We show that vorinostat only inhibits proliferation of BCC cells in vitro and BCC allografts in vivo at high dose, limiting its usefulness as a monotherapy...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29092942/pdx-mi-minimal-information-for-patient-derived-tumor-xenograft-models
#11
Terrence F Meehan, Nathalie Conte, Theodore Goldstein, Giorgio Inghirami, Mark A Murakami, Sebastian Brabetz, Zhiping Gu, Jeffrey A Wiser, Patrick Dunn, Dale A Begley, Debra M Krupke, Andrea Bertotti, Alejandra Bruna, Matthew H Brush, Annette T Byrne, Carlos Caldas, Amanda L Christie, Dominic A Clark, Heidi Dowst, Jonathan R Dry, James H Doroshow, Olivier Duchamp, Yvonne A Evrard, Stephane Ferretti, Kristopher K Frese, Neal C Goodwin, Danielle Greenawalt, Melissa A Haendel, Els Hermans, Peter J Houghton, Jos Jonkers, Kristel Kemper, Tin O Khor, Michael T Lewis, K C Kent Lloyd, Jeremy Mason, Enzo Medico, Steven B Neuhauser, James M Olson, Daniel S Peeper, Oscar M Rueda, Je Kyung Seong, Livio Trusolino, Emilie Vinolo, Robert J Wechsler-Reya, David M Weinstock, Alana Welm, S John Weroha, Frédéric Amant, Stefan M Pfister, Marcel Kool, Helen Parkinson, Atul J Butte, Carol J Bult
Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29057876/comprehensive-analysis-of-normal-adjacent-to-tumor-transcriptomes
#12
Dvir Aran, Roman Camarda, Justin Odegaard, Hyojung Paik, Boris Oskotsky, Gregor Krings, Andrei Goga, Marina Sirota, Atul J Butte
Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies. However, little is known about the transcriptomic profile of NAT, how it is influenced by the tumor, and how the profile compares with non-tumor-bearing tissues. Here, we integrate data from the Genotype-Tissue Expression project and The Cancer Genome Atlas to comprehensively analyze the transcriptomes of healthy, NAT, and tumor tissues in 6506 samples across eight tissues and corresponding tumor types...
October 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28925997/precision-annotation-of-digital-samples-in-ncbi-s-gene-expression-omnibus
#13
Dexter Hadley, James Pan, Osama El-Sayed, Jihad Aljabban, Imad Aljabban, Tej D Azad, Mohamad O Hadied, Shuaib Raza, Benjamin Abhishek Rayikanti, Bin Chen, Hyojung Paik, Dvir Aran, Jordan Spatz, Daniel Himmelstein, Maryam Panahiazar, Sanchita Bhattacharya, Marina Sirota, Mark A Musen, Atul J Butte
The Gene Expression Omnibus (GEO) contains more than two million digital samples from functional genomics experiments amassed over almost two decades. However, individual sample meta-data remains poorly described by unstructured free text attributes preventing its largescale reanalysis. We introduce the Search Tag Analyze Resource for GEO as a web application (http://STARGEO.org) to curate better annotations of sample phenotypes uniformly across different studies, and to use these sample annotations to define robust genomic signatures of disease pathology by meta-analysis...
September 19, 2017: Scientific Data
https://www.readbyqxmd.com/read/28699633/reversal-of-cancer-gene-expression-correlates-with-drug-efficacy-and-reveals-therapeutic-targets
#14
Bin Chen, Li Ma, Hyojung Paik, Marina Sirota, Wei Wei, Mei-Sze Chua, Samuel So, Atul J Butte
The decreasing cost of genomic technologies has enabled the molecular characterization of large-scale clinical disease samples and of molecular changes upon drug treatment in various disease models. Exploring methods to relate diseases to potentially efficacious drugs through various molecular features is critically important in the discovery of new therapeutics. Here we show that the potency of a drug to reverse cancer-associated gene expression changes positively correlates with that drug's efficacy in preclinical models of breast, liver and colon cancers...
July 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28667073/cancer-cell-autonomous-parainflammation-mimics-immune-cell-infiltration
#15
Audrey Lasry, Dvir Aran, Atul J Butte, Yinon Ben-Neriah
Parainflammation is a unique variant of inflammation, characterized by epithelial-autonomous activation of inflammatory response. Parainflammation has been shown to strongly promote mouse gut tumorigenesis upon p53 loss. In a recent study, we explored the prevalence of parainflammation in human cancer and determined its relationship to certain molecular and clinical parameters affecting treatment and prognosis. Parainflammation can be identified from a 40-gene signature and is found in both carcinoma cell lines and a variety of primary tumors, independently of tumor microenvironment...
July 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in%C3%A2-vitro-and-in-mice-by-inhibiting-cell-division-cycle-37-signaling
#16
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of messenger RNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are down-regulated in HCCs and reduce expression of genes up-regulated in HCCs using a nonparametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
June 2017: Gastroenterology
https://www.readbyqxmd.com/read/28212683/evidence-for-benefit-of-statins-to-modify-cognitive-decline-and-risk-in-alzheimer-s-disease
#17
Nophar Geifman, Roberta Diaz Brinton, Richard E Kennedy, Lon S Schneider, Atul J Butte
BACKGROUND: Despite substantial research and development investment in Alzheimer's disease (AD), effective therapeutics remain elusive. Significant emerging evidence has linked cholesterol, β-amyloid and AD, and several studies have shown a reduced risk for AD and dementia in populations treated with statins. However, while some clinical trials evaluating statins in general AD populations have been conducted, these resulted in no significant therapeutic benefit. By focusing on subgroups of the AD population, it may be possible to detect endotypes responsive to statin therapy...
February 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28057685/rimmport-an-r-bioconductor-package-that-enables-ready-for-analysis-immunology-research-data
#18
Ravi D Shankar, Sanchita Bhattacharya, Chethan Jujjavarapu, Sandra Andorf, Jeffery A Wiser, Atul J Butte
Summary: : Open access to raw clinical and molecular data related to immunological studies has created a tremendous opportunity for data-driven science. We have developed RImmPort that prepares NIAID-funded research study datasets in ImmPort (immport.org) for analysis in R. RImmPort comprises of three main components: (i) a specification of R classes that encapsulate study data, (ii) foundational methods to load data of a specific study and (iii) generic methods to slice and dice data across different dimensions in one or more studies...
April 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/27986392/solving-immunology
#19
REVIEW
Yoram Vodovotz, Ashley Xia, Elizabeth L Read, Josep Bassaganya-Riera, David A Hafler, Eduardo Sontag, Jin Wang, John S Tsang, Judy D Day, Steven H Kleinstein, Atul J Butte, Matthew C Altman, Ross Hammond, Stuart C Sealfon
Emergent responses of the immune system result from the integration of molecular and cellular networks over time and across multiple organs. High-content and high-throughput analysis technologies, concomitantly with data-driven and mechanistic modeling, hold promise for the systematic interrogation of these complex pathways. However, connecting genetic variation and molecular mechanisms to individual phenotypes and health outcomes has proven elusive. Gaps remain in data, and disagreements persist about the value of mechanistic modeling for immunology...
February 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27863422/in-silico-and-in-vitro-drug-screening-identifies-new-therapeutic-approaches-for-ewing-sarcoma
#20
Ziyan Y Pessetto, Bin Chen, Hani Alturkmani, Stephen Hyter, Colleen A Flynn, Michael Baltezor, Yan Ma, Howard G Rosenthal, Kathleen A Neville, Scott J Weir, Atul J Butte, Andrew K Godwin
The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches...
January 17, 2017: Oncotarget
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