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Atul Butte

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 12, 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...
October 4, 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: .
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...
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...
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...
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
Jacob J Hughey, Trevor Hastie, Atul J Butte
Numerous biological systems oscillate over time or space. Despite these oscillators' importance, data from an oscillatory system is problematic for existing methods of regularized supervised learning. We present ZeitZeiger, a method to predict a periodic variable (e.g. time of day) from a high-dimensional observation. ZeitZeiger learns a sparse representation of the variation associated with the periodic variable in the training observations, then uses maximum-likelihood to make a prediction for a test observation...
May 5, 2016: Nucleic Acids Research
Jernej Godec, Yan Tan, Arthur Liberzon, Pablo Tamayo, Sanchita Bhattacharya, Atul J Butte, Jill P Mesirov, W Nicholas Haining
Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology...
January 19, 2016: Immunity
Nophar Geifman, Atul J Butte
Open clinical trial data offer many opportunities for the scientific community to independently verify published results, evaluate new hypotheses and conduct meta-analyses. These data provide a springboard for scientific advances in precision medicine but the question arises as to how representative clinical trials data are of cancer patients overall. Here we present the integrative analysis of data from several cancer clinical trials and compare these to patient-level data from The Cancer Genome Atlas (TCGA)...
2016: Pacific Symposium on Biocomputing
Xiaoyuan Li, Juan Kang, Qi Pan, Weronika Sikora-Wohlfeld, Dachun Zhao, Changting Meng, Chunmei Bai, Anil Patwardhan, Richard Chen, Hong Ren, Atul J Butte, Keyue Ding
To identify rare mutations and retrospectively estimate the cancer risk of a 45-year old female patient diagnosed with Li-Fraumeni syndrome (LFS), who developed nine primary malignant neoplasms in a period of 38 years, we conducted next-generation sequencing in this patient. Whole-genome and whole-exome sequencing were performed in DNA of whole blood obtained a year prior to the diagnosis of acute myeloid leukemia (AML) and at the time of diagnosis of AML, respectively. We analyzed rare mutations in cancer susceptibility genes using a candidate strategy and estimated cancer risk using the Risk-O-Gram algorithm...
March 2016: Oncology Reports
Nophar Geifman, Sanchita Bhattacharya, Atul J Butte
OBJECTIVE: Cytokines play a central role in both health and disease, modulating immune responses and acting as diagnostic markers and therapeutic targets. This work takes a systems-level approach for integration and examination of immune patterns, such as cytokine gene expression with information from biomedical literature, and applies it in the context of disease, with the objective of identifying potentially useful relationships and areas for future research. RESULTS: We present herein the integration and analysis of immune-related knowledge, namely, information derived from biomedical literature and gene expression arrays...
May 2016: Journal of the American Medical Informatics Association: JAMIA
B Chen, A J Butte
The advances of genomics, sequencing, and high throughput technologies have led to the creation of large volumes of diverse datasets for drug discovery. Analyzing these datasets to better understand disease and discover new drugs is becoming more common. Recent open data initiatives in basic and clinical research have dramatically increased the types of data available to the public. The past few years have witnessed successful use of big data in many sectors across the whole drug discovery pipeline. In this review, we will highlight the state of the art in leveraging big data to identify new targets, drug indications, and drug response biomarkers in this era of precision medicine...
March 2016: Clinical Pharmacology and Therapeutics
Dvir Aran, Marina Sirota, Atul J Butte
The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results. Here we present a systematic analysis using different measurement modalities of tumour purity in >10,000 samples across 21 cancer types from the Cancer Genome Atlas...
2015: Nature Communications
Nophar Geifman, Jennifer Bollyky, Sanchita Bhattacharya, Atul J Butte
Data generated by the numerous clinical trials conducted annually worldwide have the potential to be extremely beneficial to the scientific and patient communities. This potential is well recognized and efforts are being made to encourage the release of raw patient-level data from these trials to the public. The issue of sharing clinical trial data has recently gained attention, with many agreeing that this type of data should be made available for research in a timely manner. The availability of clinical trial data is most important for study reproducibility, meta-analyses, and improvement of study design...
November 11, 2015: BMC Medicine
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