Institute for Genomics and Systems Biology

Chicago, IL, United States

Institute for Genomics and Systems Biology

Chicago, IL, United States
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Wilke A.,Argonne National Laboratory | Wilke A.,University of Chicago | Harrison T.,Argonne National Laboratory | Harrison T.,University of Chicago | And 8 more authors.
BMC Bioinformatics | Year: 2012

Background: Computing of sequence similarity results is becoming a limiting factor in metagenome analysis. Sequence similarity search results encoded in an open, exchangeable format have the potential to limit the needs for computational reanalysis of these data sets. A prerequisite for sharing of similarity results is a common reference.Description: We introduce a mechanism for automatically maintaining a comprehensive, non-redundant protein database and for creating a quarterly release of this resource. In addition, we present tools for translating similarity searches into many annotation namespaces, e.g. KEGG or NCBI's GenBank.Conclusions: The data and tools we present allow the creation of multiple result sets using a single computation, permitting computational results to be shared between groups for large sequence data sets. © 2012 Wilke et al.; licensee BioMed Central Ltd.

News Article | November 8, 2016

High quality proteins are critical for contemporary biomedical research. Biochemists and biophysicists require high quality proteins to probe the molecular mechanisms of proteins in their native state. Proteomics researchers, cell biologists, and pathologists require high-quality antibodies as purification tools and as diagnostic reagents. Formulation scientists need to quickly gain an understanding of the impact that buffer and other components have on the structure and function of protein biologics. In this webinar, several complementary protein analysis tools will be introduced and discussed, including chromatography, UV/VIS spectroscopy, light scattering, electrophoresis, western blotting and analytical ultracentrifugation. Participants can expect a discuss of measuring the pairwise interaction matrices of hundreds of ErbB signaling proteins and peptides to illustrate the importance of quality control in obtaining high quality protein interaction data. During the course of this free webinar, sponsored by Beckman Coulter, participants will gain a better grasp the tools available and when each might best be employed in daily research activities, including best approaches for the purification and quality analysis of proteins and antibodies. Systematic methods for assessing interaction potentials of proteins will also be discussed, as well as methods for higher-throughput western blotting. Dr. Rich Jones, senior marketing manager at Beckman Coulter, will be the speaker for this webinar. Jones has a long-standing interest in the development and application of automated protein analysis technologies and workflows for interrogating protein systems in human biology and pharmacology. Jones has more than 20 years of experience in the field of protein and cell biotechnology. He received his doctorate in biochemistry and cancer biology from Texas A&M University, followed by postdoctoral work in systems biochemistry from Harvard University where he participated in the development of protein microarray approaches for mapping human protein interaction networks in breast cancer. In addition to being an assistant professor at The University of Chicago, he was a Core Fellow and founding member of the Institute for Genomics and Systems Biology and was founder and director of the University of Chicago Micro-western array Protein Analysis Core Facility. LabRoots will host the webinar on November 10, 2016, beginning at 7:30 a.m. PT, 10:30 a.m. ET. To learn about this webinar, continuing education credits or to register for free, click here. About Beckman Coulter: Beckman Coulter serves customers in two segments: Diagnostics and Life Sciences. The company develops, manufactures, and markets products that simplify, automate, and innovate complex biomedical testing. More than 275,000 Beckman Coulter systems operate in both Diagnostics and Life Sciences laboratories on seven continents. Scientists use Beckman Coulter’s Life Science research instruments to study complex biological problems, including causes of disease and potential new therapies or drugs. About LabRoots: LabRoots is the leading scientific social networking website and producer of educational virtual events and webinars. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the world’s largest series of virtual events within the Life Sciences and Clinical Diagnostics community.

Xu J.,University of California at San Francisco | Haigis K.M.,Massachusetts General Hospital | Firestone A.J.,University of California at San Francisco | McNerney M.E.,Institute for Genomics and Systems Biology | And 8 more authors.
Cancer Discovery | Year: 2013

Biochemical properties of Ras oncoproteins and their transforming ability strongly support a dominant mechanism of action in tumorigenesis. However, genetic studies unexpectedly suggested that wild-type (WT) Ras exerts tumor suppressor activity. Expressing oncogenic NrasG12D in the hematopoietic compartment of mice induces an aggressive myeloproliferative neoplasm that is exacerbated in homozygous mutant animals. Here, we show that increased NrasG12D gene dosage, but not inactivation of WT Nras, underlies the aggressive in vivo behavior of NrasG12D/G12D hematopoietic cells. Modulating NrasG12D dosage had discrete effects on myeloid progenitor growth, signal transduction, and sensitivity to MAP-ERK kinase (MEK) inhibition. Furthermore, enforced WT N-Ras expression neither suppressed the growth of Nras -mutant cells nor inhibited myeloid transformation by exogenous NrasG12D. Importantly, NRAS expression increased in human cancer cell lines with NRAS mutations. These data have therapeutic implications and support reconsidering the proposed tumor suppressor activity of WT Ras in other cancers. SIGNIFICANCE: Understanding the mechanisms of Ras -induced transformation and adaptive cellular responses is fundamental. The observation that oncogenic Nras lacks tumor suppressor activity, whereas increased dosage strongly modulates cell growth and alters sensitivity to MEK inhibition, suggests new therapeutic opportunities in cancer. © 2013 American Association for Cancer Research.

Keegan K.P.,Argonne National Laboratory | Keegan K.P.,University of Chicago | Keegan K.P.,Institute for Genomics and Systems Biology | Trimble W.L.,Argonne National Laboratory | And 15 more authors.
PLoS Computational Biology | Year: 2012

We provide a novel method, DRISEE (duplicate read inferred sequencing error estimation), to assess sequencing quality (alternatively referred to as "noise" or "error") within and/or between sequencing samples. DRISEE provides positional error estimates that can be used to inform read trimming within a sample. It also provides global (whole sample) error estimates that can be used to identify samples with high or varying levels of sequencing error that may confound downstream analyses, particularly in the case of studies that utilize data from multiple sequencing samples. For shotgun metagenomic data, we believe that DRISEE provides estimates of sequencing error that are more accurate and less constrained by technical limitations than existing methods that rely on reference genomes or the use of scores (e.g. Phred). Here, DRISEE is applied to (non amplicon) data sets from both the 454 and Illumina platforms. The DRISEE error estimate is obtained by analyzing sets of artifactual duplicate reads (ADRs), a known by-product of both sequencing platforms. We present DRISEE as an open-source, platform-independent method to assess sequencing error in shotgun metagenomic data, and utilize it to discover previously uncharacterized error in de novo sequence data from the 454 and Illumina sequencing platforms. © 2012 Keegan et al.

Barriere A.,Institute for Genomics and Systems Biology | Gordon K.L.,University of Chicago | Ruvinsky I.,Institute for Genomics and Systems Biology | Ruvinsky I.,University of Chicago
PLoS Genetics | Year: 2011

Different functional constraints contribute to different evolutionary rates across genomes. To understand why some sequences evolve faster than others in a single cis-regulatory locus, we investigated function and evolutionary dynamics of the promoter of the Caenorhabditis elegans unc-47 gene. We found that this promoter consists of two distinct domains. The proximal promoter is conserved and is largely sufficient to direct appropriate spatial expression. The distal promoter displays little if any conservation between several closely related nematodes. Despite this divergence, sequences from all species confer robustness of expression, arguing that this function does not require substantial sequence conservation. We showed that even unrelated sequences have the ability to promote robust expression. A prominent feature shared by all of these robustness-promoting sequences is an AT-enriched nucleotide composition consistent with nucleosome depletion. Because general sequence composition can be maintained despite sequence turnover, our results explain how different functional constraints can lead to vastly disparate rates of sequence divergence within a promoter. © 2011 Barrière et al.

Leone V.,University of Chicago | Gibbons S.M.,Institute for Genomics and Systems Biology | Gibbons S.M.,University of Chicago | Martinez K.,University of Chicago | And 18 more authors.
Cell Host and Microbe | Year: 2015

Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts. Examination of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet. © 2015 Elsevier Inc.

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