Systems Biology Commons^™

Micom: Metagenome-Scale Modeling To Infer Metabolic Interactions In The Gut Microbiota., Christian Diener, Sean M Gibbons, Osbaldo Resendis-Antonio

Articles, Abstracts, and Reports

Compositional changes in the gut microbiota have been associated with a variety of medical conditions such as obesity, Crohn's disease, and diabetes. However, connecting microbial community composition to ecosystem function remains a challenge. Here, we introduce MICOM, a customizable metabolic model of the human gut microbiome. By using a heuristic optimization approach based on L2 regularization, we were able to obtain a unique set of realistic growth rates that corresponded well with observed replication rates. We integrated adjustable dietary and taxon abundance constraints to generate personalized metabolic models for individual metagenomic samples. We applied MICOM to a balanced cohort of …

Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane

Biostatistics Faculty Publications

Introduction—We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.

Methods—We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions.

Results—We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ …

Acclimation, Adaptation, Traits And Trade-Offs In Plankton Functional Type Models: Reconciling Terminology For Biology And Modelling, Kevin J. Flynn, Michael St. John, John A. Raven, David O. F. Skibinski, J. Icarus Allen, Aditee Mitra, Eileen E. Hofmann

CCPO Publications

We propose definitions in terminology to enhance ongoing collaborations between biologists and modellers on plankton ecology. Organism "functional type" should refer to commonality in ecology not biogeochemistry; the latter is largely an emergent property of the former, while alignment with ecology is also consistent with usage in terrestrial science. Adaptation should be confined, as in genetics, to consideration of species inter-generational change; most so-called "adaptive" plankton models are thus acclimative, modifying vital rates in response to stimuli. Trait trade-off approaches should ideally only be considered for describing intra-generational interactions; in applications between generations, and certainly between unrelated species, such concepts …

Identification Of Yeast Cell Cycle Regulated Genes Based On Genomic Features, Chao Cheng, Yao Fu, Linsheng Shen, Mark Gerstein

Dartmouth Scholarship

Background: Time-course microarray experiments have been widely used to identify cell cycle regulated genes. However, the method is not effective for lowly expressed genes and is sensitive to experimental conditions. To complement microarray experiments, we propose a computational method to predict cell cycle regulated genes based on their genomic features – transcription factor binding and motif profiles.

Results: Through integrating gene-expression data with ChIP-chip binding and putative binding sites of transcription factors, our method shows high accuracy in discriminating yeast cell cycle regulated genes from non-cell cycle regulated ones. We predict 211 novel cell cycle regulated genes. Our model rediscovers …

The Hyperthermophilic Archaeon Sulfolobus: From Exploration To Exploitation, Stan J.J. Brouns, Thijs J.G. Ettema, Kenneth M. Stedman, Jasper Walther, Hauke Smith, Ambrosius P.L. Snijders, Mark Young, Rolf Bernander, Phillip C. Wright, Betina Siebers, John Van Der Oost

Biology Faculty Publications and Presentations

In the early 1970s, Sulfolobus was first isolated by Thomas Brock and co-workers from sulfur-rich acidic hot springs in Yellowstone National Park. Sulfolobus became one of the model organisms of Archaea in general, and of Crenarchaea in particular. Many of its unusual physiological characteristics have been investigated, and several of its thermostable enzymes have been studied in considerable detail. For fundamental reasons, and because of its potential for industrial applications, Sulfolobus has been selected for a genome sequence project. The recent completion of the Sulfolobus solfataricus genome has set the stage for a series of postgenome research lines that will …