Institution
Institute for Systems Biology
Nonprofit•Seattle, Washington, United States•
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.
Topics: Population, Proteomics, Gene, Proteome, Systems biology
Papers published on a yearly basis
Papers
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TL;DR: This work utilizes Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines, to provide a general approach in spatially-resolved single cell metabolomics studies.
Abstract: Non-invasively probing metabolites within single live cells is highly desired but challenging. Here we utilize Raman spectro-microscopy for spatial mapping of metabolites within single cells, with the specific goal of identifying druggable metabolic susceptibilities from a series of patient-derived melanoma cell lines. Each cell line represents a different characteristic level of cancer cell de-differentiation. First, with Raman spectroscopy, followed by stimulated Raman scattering (SRS) microscopy and transcriptomics analysis, we identify the fatty acid synthesis pathway as a druggable susceptibility for differentiated melanocytic cells. We then utilize hyperspectral-SRS imaging of intracellular lipid droplets to identify a previously unknown susceptibility of lipid mono-unsaturation within de-differentiated mesenchymal cells with innate resistance to BRAF inhibition. Drugging this target leads to cellular apoptosis accompanied by the formation of phase-separated intracellular membrane domains. The integration of subcellular Raman spectro-microscopy with lipidomics and transcriptomics suggests possible lipid regulatory mechanisms underlying this pharmacological treatment. Our method should provide a general approach in spatially-resolved single cell metabolomics studies.
66 citations
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TL;DR: In this article, error growth techniques from nonlinear dynamics are used to estimate the variance of a system around a steady-state attractor, and it is shown that variablity due to intrinsic stochasticity is directly linked to the stability of the steady state, and therefore to the system's resistance to external perturbations.
66 citations
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TL;DR: The health care community must join forces with patients to quantify wellness, define disease transitions, and reduce the cost of health care.
Abstract: Unsustainable cost increases threaten the global health care system, and further progress is stymied more by societal than technological factors. Only by engaging health care consumers (that is, patients) as pioneers who provide both health-related data and insights into pathophysiology can we meet
66 citations
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TL;DR: It is shown that host cells infected with L. amazonensis upregulate transcription of LYST/Beige, which was previously shown to regulate lysosome size, and this upregulation functions as a host innate response to limit parasite growth.
Abstract: The intracellular protozoan Leishmania replicates in parasitophorous vacuoles (PV) that share many features with late endosomes/lysosomes. L. amazonensis PVs expand markedly during infections, but the impact of PV size on parasite intracellular survival is still unknown. Here we show that host cells infected with L. amazonensis upregulate transcription of LYST/Beige, which was previously shown to regulate lysosome size. Mutations in LYST/Beige caused further PV expansion and enhanced L. amazonensis replication. In contrast, LYST/Beige overexpression led to small PVs that did not sustain parasite growth. Treatment of LYST/Beige over-expressing cells with vacuolin-1 reversed this phenotype, expanding PVs and promoting parasite growth. The opposite was seen with E-64d, which reduced PV size in LYST-Beige mutant cells and inhibited L. amazonensis replication. Enlarged PVs appear to protect parasites from oxidative damage, since inhibition of nitric oxide synthase had no effect on L. amazonensis viability within large PVs, but enhanced their growth within LYST/Beige-induced small PVs. Thus, the upregulation of LYST/Beige in infected cells functions as a host innate response to limit parasite growth, by reducing PV volume and inhibiting intracellular survival.
65 citations
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TL;DR: Stratification of a large dataset of 254 HPC families supports the existence of multiple HPC loci, whose presence may be best identified by analyses of large, including pooled, datasets which consider locus heterogeneity.
Abstract: Hereditary prostate cancer (HPC) is a genetically heterogeneous disease, complicating efforts to map and clone susceptibility loci. We have used stratification of a large dataset of 254 HPC families in an effort to improve power to detect HPC loci and to understand what types of family features may improve locus identification. The strongest result is that of a dominant locus at 6p22.3 (heterogeneity LOD (HLOD) = 2.51), the evidence for which is increased by consideration of the age of PC onset (HLOD = 3.43 in 214 families with median age-of-onset 56-72 years) and co-occurrence of primary brain cancer (HLOD = 2.34 in 21 families) in the families. Additional regions for which we observe modest evidence for linkage include chromosome 7q and 17p. Only weak evidence of several previously implicated HPC regions is detected. These analyses support the existence of multiple HPC loci, whose presence may be best identified by analyses of large, including pooled, datasets which consider locus heterogeneity.
65 citations
Authors
Showing all 1292 results
Name | H-index | Papers | Citations |
---|---|---|---|
Younan Xia | 216 | 943 | 175757 |
Ruedi Aebersold | 182 | 879 | 141881 |
David Haussler | 172 | 488 | 224960 |
Steven P. Gygi | 172 | 704 | 129173 |
Nahum Sonenberg | 167 | 647 | 104053 |
Leroy Hood | 158 | 853 | 128452 |
Mark H. Ellisman | 117 | 637 | 55289 |
Wei Zhang | 112 | 1189 | 93641 |
John Ralph | 109 | 442 | 39238 |
Eric H. Davidson | 106 | 454 | 47058 |
James R. Heath | 103 | 425 | 58548 |
Alan Aderem | 99 | 246 | 46682 |
Anne-Claude Gingras | 97 | 336 | 40714 |
Trey Ideker | 97 | 306 | 72276 |
Michael H. Gelb | 94 | 506 | 34714 |