Biology subjects

Mundt, F.

Publications and source records attributed to Mundt, F..

2 recordsLinked to original sources

bioRxiv2020

Clinical Knowledge Graph Integrates Proteomics Data into Clinical Decision-Making

The promise of precision medicine is to deliver personalized treatment based on the unique physiology of each patient. This concept was fueled by the genomic revolution, but it is now evident that integrating other types of omics data, like proteomics, into the clinical decision-making process will be essential to accomplish precision medicine goals. However, quantity and diversity of biomedical data, and the spread of clinically relevant knowledge across myriad biomedical databases and publications makes this exceptionally difficult. To address this, we developed the Clinical Knowledge Graph (CKG), an open source platform currently comprised of more than 16 million nodes and 220 million relationships to represent relevant experimental data, public databases and the literature. The CKG also incorporates the latest statistical and machine learning algorithms, drastically accelerating analysis and interpretation of typical proteomics workflows. We use several biomarker studies to illustrate how the CKG may support, enrich and accelerate clinical decision-making. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/084897v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@433689org.highwire.dtl.DTLVardef@b18068org.highwire.dtl.DTLVardef@1656084org.highwire.dtl.DTLVardef@a38201_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2020

Mapping the unique and shared functions of oncogenic KRAS and RIT1 with proteome and transcriptome profiling

Aberrant activation of RAS oncogenes is prevalent in lung adenocarcinoma, with somatic mutation of KRAS occurring in [~]30% of tumors. Recently, we identified somatic mutation of the RAS-family GTPase RIT1 in lung adenocarcinoma, but relatively little is known about the biological pathways regulated by RIT1 and how these relate to the oncogenic KRAS network. Here we present quantitative proteomic and transcriptomic profiles from KRAS-mutant and RIT1-mutant isogenic lung epithelial cells and globally characterize the signaling networks regulated by each oncogene. We find that both mutant KRAS and mutant RIT1 promote S6 kinase, AKT, and RAF/MEK signaling, and promote epithelial-to-mesenchymal transition and immune evasion via HLA protein loss. However, KRAS and RIT1 diverge in regulation of phosphorylation sites on EGFR, USO1, and AHNAK proteins. The majority of the proteome changes are related to altered transcriptional regulation, but a small subset of proteins are differentially regulated by both oncoproteins at the post-transcriptional level, including intermediate filament proteins, metallothioneins, and MHC Class I proteins. These data provide the first global, unbiased characterization of oncogenic RIT1 network and identify the shared and divergent functions of oncogenic RIT1 and KRAS GTPases in lung cancer.

cancer biology↗