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Atul Butte

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
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
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
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
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 ( 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
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...
December 13, 2016: Trends in Immunology
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
Atul J Butte
No abstract text is available yet for this article.
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
Shai S Shen-Orr, David Furman, Brian A Kidd, Francois Hadad, Patricia Lovelace, Ying-Wen Huang, Yael Rosenberg-Hasson, Sally Mackey, Fatemeh A Gomari Grisar, Yishai Pickman, Holden T Maecker, Yueh-Hsiu Chien, Cornelia L Dekker, Joseph C Wu, Atul J Butte, Mark M Davis
Chronic inflammation, a decline in immune responsiveness, and reduced cardiovascular function are all associated with aging, but the relationships among these phenomena remain unclear. Here, we longitudinally profiled a total of 84 signaling conditions in 91 young and older adults and observed an age-related reduction in cytokine responsiveness within four immune cell lineages, most prominently T cells. The phenotype can be partially explained by elevated baseline levels of phosphorylated STAT (pSTAT) proteins and a different response capacity of naive versus memory T cell subsets to interleukin 6 (IL-6), interferon α (IFN-α), and, to a lesser extent, IL-21 and IFN-γ...
October 26, 2016: Cell Systems
Jacob J Hughey, Atul J Butte
The daily timing of mammalian physiology is coordinated by circadian clocks throughout the body. Although measurements of clock gene expression indicate that these clocks in mice are normally in phase with each other, the situation in humans remains unclear. We used publicly available data from five studies, comprising over 1000 samples, to compare the phasing of circadian gene expression in human brain and human blood. Surprisingly, after controlling for age, clock gene expression in brain was phase-delayed by ~8...
December 2016: Journal of Biological Rhythms
Dvir Aran, Atul J Butte
Understanding a tumor's complex cellular heterogeneity will be crucial for the development of better treatment strategies. A new study suggests a novel method for the in silico dissociation of solid tumors and presents novel insights that have implications for immunotherapy in cancer.Please see the related Research article: .
August 22, 2016: Genome Biology
Dvir Aran, Audrey Lasry, Adar Zinger, Moshe Biton, Eli Pikarsky, Asaf Hellman, Atul J Butte, Yinon Ben-Neriah
BACKGROUND: Chronic inflammation has been recognized as one of the hallmarks of cancer. We recently showed that parainflammation, a unique variant of inflammation between homeostasis and chronic inflammation, strongly promotes mouse gut tumorigenesis upon p53 loss. Here we explore the prevalence of parainflammation in human cancer and determine its relationship to certain molecular and clinical parameters affecting treatment and prognosis. RESULTS: We generated a transcriptome signature to identify parainflammation in many primary human tumors and carcinoma cell lines as distinct from their normal tissue counterparts and the tumor microenvironment and show that parainflammation-positive tumors are enriched for p53 mutations and associated with poor prognosis...
July 8, 2016: Genome Biology
Melina Amor, Veronica Moreno-Viedma, Alisina Sarabi, Nicole G Grün, Bianca Itariu, Lukas Leitner, Irene Steiner, Martin Bilban, Keiichi Kodama, Atul J Butte, Guenther Staffler, Maximilian Zeyda, Thomas M Stulnig
Obesity is strongly associated with metabolic syndrome, a combination of risk factors that predispose to the development of the cardiometabolic diseases: atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Prevention of metabolic syndrome requires novel interventions to address this health challenge. The objective of this study was the identification of candidate molecules for the prevention and treatment of insulin resistance and atherosclerosis, conditions that underlie type 2 diabetes mellitus and cardiovascular disease, respectively...
June 30, 2016: Molecular Medicine
Robert C Rennert, Michael Januszyk, Michael Sorkin, Melanie Rodrigues, Zeshaan N Maan, Dominik Duscher, Alexander J Whittam, Revanth Kosaraju, Michael T Chung, Kevin Paik, Alexander Y Li, Michael Findlay, Jason P Glotzbach, Atul J Butte, Geoffrey C Gurtner
Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles...
June 21, 2016: Nature Communications
Idit Kosti, Nishant Jain, Dvir Aran, Atul J Butte, Marina Sirota
The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples...
May 4, 2016: Scientific Reports
H Craig Mak
Atul Butte discusses large patient cohorts, non-genomic factors in precision medicine, mobile devices, and the outsourcing of experimental work.
October 28, 2015: Cell Systems
Steven C Bagley, Marina Sirota, Richard Chen, Atul J Butte, Russ B Altman
Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1...
April 2016: PLoS Computational Biology
Chase Romere, Clemens Duerrschmid, Juan Bournat, Petra Constable, Mahim Jain, Fan Xia, Pradip K Saha, Maria Del Solar, Bokai Zhu, Brian York, Poonam Sarkar, David A Rendon, M Waleed Gaber, Scott A LeMaire, Joseph S Coselli, Dianna M Milewicz, V Reid Sutton, Nancy F Butte, David D Moore, Atul R Chopra
Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation...
April 21, 2016: Cell
Keiichi Kodama, Zhiyuan Zhao, Kyoko Toda, Linda Yip, Rebecca Fuhlbrigge, Dongmei Miao, C Garrison Fathman, Satoru Yamada, Atul J Butte, Liping Yu
Type 1 diabetes (T1D) is caused by autoreactive T cells that recognize pancreatic islet antigens and destroy insulin-producing β-cells. This attack results from a breakdown in tolerance for self-antigens, which is controlled by ectopic antigen expression in the thymus and pancreatic lymph nodes (PLNs). The autoantigens known to be involved include a set of islet proteins, such as insulin, GAD65, IA-2, and ZnT8. In an attempt to identify additional antigenic proteins, we performed an expression-based genome-wide association study using microarray data from 118 arrays of the thymus and PLNs of T1D mice...
May 2016: Diabetes
Dvir Aran, Marina Sirota, Atul J Butte
No abstract text is available yet for this article.
2016: Nature Communications
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