Institute for Systems Biology

About: Institute for Systems Biology is a nonprofit organization based out in Seattle, Washington, United States. It is known for research contribution in the topics: Population & Proteomics. The organization has 1277 authors who have published 2777 publications receiving 353165 citations.

SBEAMS-Microarray: database software supporting genomic expression analyses for systems biology.

Abstract: Background The biological information in genomic expression data can be understood, and computationally extracted, in the context of systems of interacting molecules. The automation of this information extraction requires high throughput management and analysis of genomic expression data, and integration of these data with other data types.

A stress test for mass spectrometry–based proteomics

Abstract: A multilaboratory study attempts to dispel some of the notions of the irreproducibility of mass spectrometry–based proteomics by pinpointing where the methodological problems are and where challenges remain.

Do genome-scale models need exact solvers or clearer standards?

Abstract: Constraint‐based analysis of genome‐scale models (GEMs) arose shortly after the first genome sequences became available. As numerous reviews of the field show, this approach and methodology has proven to be successful in studying a wide range of biological phenomena (McCloskey et al, 2013; Bordbar et al, 2014). However, efforts to expand the user base are impeded by hurdles in correctly formulating these problems to obtain numerical solutions. In particular, in a study entitled “An exact arithmetic toolbox for a consistent and reproducible structural analysis of metabolic network models” (Chindelevitch et al, 2014), the authors apply an exact solver to 88 genome‐scale constraint‐based models of metabolism. The authors claim that COBRA calculations (Orth et al, 2010) are inconsistent with their results and that many published and actively used (Lee et al, 2007; McCloskey et al, 2013) genome‐scale models do support cellular growth in existing studies only because of numerical errors. They base these broad claims on two observations: (i) three reconstructions (iAF1260, iIT341, and iNJ661) compute feasibly in COBRA, but are infeasible when exact numerical algorithms are used by their software (entitled MONGOOSE); (ii) linear programs generated by MONGOOSE for iIT341 were submitted to the NEOS Server (a Web site that runs linear programs through various solvers) and gave inconsistent results. They further claim that a large percentage of these COBRA models are actually unable to produce biomass flux. Here, we demonstrate that the claims made by Chindelevitch et al (2014) stem from an incorrect parsing of models from files rather than actual problems with numerical error or COBRA computations.

Hydra: a scalable proteomic search engine which utilizes the Hadoop distributed computing framework

Abstract: Background For shotgun mass spectrometry based proteomics the most computationally expensive step is in matching the spectra against an increasingly large database of sequences and their post-translational modifications with known masses. Each mass spectrometer can generate data at an astonishingly high rate, and the scope of what is searched for is continually increasing. Therefore solutions for improving our ability to perform these searches are needed.

Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodium vivax salivary gland sporozoites.

Abstract: Plasmodium falciparum and Plasmodium vivax cause the majority of human malaria cases. Research efforts predominantly focus on P. falciparum because of the clinical severity of infection and associated mortality rates. However, P. vivax malaria affects more people in a wider global range. Furthermore, unlike P. falciparum, P. vivax can persist in the liver as dormant hypnozoites that can be activated weeks to years after primary infection, causing relapse of symptomatic blood stages. This feature makes P. vivax unique and difficult to eliminate with the standard tools of vector control and treatment of symptomatic blood stage infection with antimalarial drugs. Infection by Plasmodium is initiated by the mosquito-transmitted sporozoite stage, a highly motile invasive cell that targets hepatocytes in the liver. The most advanced malaria vaccine for P. falciparum (RTS,S, a subunit vaccine containing of a portion of the major sporozoite surface protein) conferred limited protection in Phase III trials, falling short of WHO-established vaccine efficacy goals. However, blocking the sporozoite stage of infection in P. vivax, before the establishment of the chronic liver infection, might be an effective malaria vaccine strategy to reduce the occurrence of relapsing blood stages. It is also thought that a multivalent vaccine comprising multiple sporozoite surface antigens will provide better protection, but a comprehensive analysis of proteins in P. vivax sporozoites is not available. To inform sporozoite-based vaccine development, we employed mass spectrometry-based proteomics to identify nearly 2,000 proteins present in P. vivax salivary gland sporozoites. Analysis of protein post-translational modifications revealed extensive phosphorylation of glideosome proteins as well as regulators of transcription and translation. Additionally, the sporozoite surface proteins CSP and TRAP, which were recently discovered to be glycosylated in P. falciparum salivary gland sporozoites, were also observed to be similarly modified in P. vivax sporozoites. Quantitative comparison of the P. vivax and P. falciparum salivary gland sporozoite proteomes revealed a high degree of similarity in protein expression levels, including among invasion-related proteins. Nevertheless, orthologs with significantly different expression levels between the two species could be identified, as well as highly abundant, species-specific proteins with no known orthologs. Finally, we employed chemical labeling of live sporozoites to isolate and identify 36 proteins that are putatively surface-exposed on P. vivax salivary gland sporozoites. In addition to identifying conserved sporozoite surface proteins identified by similar analyses of other Plasmodium species, our analysis identified several as-yet uncharacterized proteins, including a putative 6-Cys protein with no known ortholog in P. falciparum.