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Biology subjects

Macias, M.

Publications and source records attributed to Macias, M..

2 recordsLinked to original sources

St. Jude Cloud a Pediatric Cancer Genomic Data Sharing Ecosystem

Effective data sharing is key to accelerating research that will improve the precision of diagnoses, efficacy of treatments and long-term survival of pediatric cancer and other childhood catastrophic diseases. We present St. Jude Cloud (https://www.stjude.cloud), a cloud-based data sharing ecosystem developed via collaboration between St. Jude Childrens Research Hospital, DNAnexus, and Microsoft, for accessing, analyzing and visualizing genomic data from >10,000 pediatric cancer patients, long-term survivors of pediatric cancer and >800 pediatric sickle cell patients. Harmonized genomic data totaling 1.25 petabyes on St. Jude Cloud include 12,104 whole genomes, 7,697 whole exomes and 2,202 transcriptomes, which are freely available to researchers worldwide. The resource is expanding rapidly with regular data uploads from St. Judes prospective clinical genomics programs, providing public access as soon as possible rather than holding data back until publication. Three interconnected apps within the St. Jude Cloud ecosystem--Genomics Platform, Pediatric Cancer Knowledgebase (PeCan) and Visualization Community--provide a unique experience for simultaneously performing advanced data analysis in the cloud and enhancing the pediatric cancer knowledgebase. We demonstrate the value of the St. Jude Cloud ecosystem through use cases that classify 48 pediatric cancer subtypes by gene expression profiling and map mutational signatures across 35 subtypes of pediatric cancer.

cancer biology

G3BP1 tethers the TSC complex to lysosomes and suppresses mTORC1 in the absence of stress granules

G3BP1 (Ras GTPase-activating protein-binding protein 1) is widely recognized as a core component of stress granules (SG), non-membranous RNA-protein-assemblies required for cellular survival under stress. We report that in the absence of SG, G3BP1 acts as lysosomal anchor of the Tuberous Sclerosis Complex (TSC) protein complex. By tethering the TSC complex to lysosomes, G3BP1 suppresses signaling through the metabolic master regulator mTORC1 (mechanistic target of rapamycin complex 1). Like the known TSC complex subunits, G3BP1 suppresses phenotypes related to mTORC1 hyperactivity in the context of tumors and neuronal dysfunction. Thus, G3BP1 is not only a core component of SG but also a key element of lysosomal TSC-mTORC1 signaling. HighlightsThe bona fide stress granule component G3BP1 O_LIis a key element of the TSC-mTORC1 signaling axis. C_LIO_LItethers the TSC complex to lysosomes. C_LIO_LIprevents mTORC1 hyperactivation by metabolic stimuli. C_LIO_LIsuppresses mTORC1-driven cancer cell motility and epileptiform activity. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/044081v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@77cb4forg.highwire.dtl.DTLVardef@c4d1a0org.highwire.dtl.DTLVardef@19e83acorg.highwire.dtl.DTLVardef@1d6a378_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology