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10.1186/s13073-018-0564-z http://scihub22266oqcxt.onion/10.1186/s13073-018-0564-z C6064051!6064051!30053901     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Genome+Med 2018 ; 10 (ä): ä Nephropedia Template TP {{tp|p=30053901|t=2018. Integrative omics analyses broaden treatment targets in human cancer |pdf=|usr=}}{{30053901}} gab.com Text Integrative omics analyses broaden treatment targets in human cancer JO: Genome Med http://www.kidney.de/pget.php?&tw=1&pmid=30053901 #FOAvip Background: Although large-scale, next-generation sequencing (NGS) studies of cancers hold promise for enabling precision oncology, challenges remain in integrating NGS with clinically validated biomarkers. Methods: To overcome such challenges, we utilized the Database of Evidence for Precision Oncology (DEPO) to link druggability to genomic, transcriptomic, and proteomic biomarkers. Using a pan-cancer cohort of 6570 tumors, we identified tumors with potentially druggable biomarkers consisting of drug-associated mutations, mRNA expression outliers, and protein/phosphoprotein expression outliers identified by DEPO. Results: Within the pan-cancer cohort of 6570 tumors, we found that 3% are druggable based on FDA-approved drug-mutation interactions in specific cancer types. However, mRNA/phosphoprotein/protein expression outliers and drug repurposing across cancer types suggest potential druggability in up to 16% of tumors. The percentage of potential drug-associated tumors can increase to 48% if we consider preclinical evidence. Further, our analyses showed co-occurring potentially druggable multi-omics alterations in 32% of tumors, indicating a role for individualized combinational therapy, with evidence supporting mTOR/PI3K/ESR1 co-inhibition and BRAF/AKT co-inhibition in 1.6 and 0.8% of tumors, respectively. We experimentally validated a subset of putative druggable mutations in BRAF identified by a protein structure-based computational tool. Finally, analysis of a large-scale drug screening dataset lent further evidence supporting repurposing of drugs across cancer types and the use of expression outliers for inferring druggability. Conclusions: Our results suggest that an integrated analysis platform can nominate multi-omics alterations as biomarkers of druggability and aid ongoing efforts to bring precision oncology to patients. Electronic supplementary material: The online version of this article (10.1186/s13073-018-0564-z) contains supplementary material, which is available to authorized users. Twit Text FOAVip Integrative omics analyses broaden treatment targets in human cancer ????Genome Med http://www.kidney.de/pget.php?&tw=1&pmid=30053901 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=30053901 #FOAvip English Wikipedia <ref>{{Cite pmid|30053901}}</ref> Integrative omics analyses broaden treatment targets in human cancer #MMPMID30053901 Sengupta S; Sun SQ; Huang Kl; Oh C; Bailey MH; Varghese R; Wyczalkowski MA; Ning J; Tripathi P; McMichael JF; Johnson KJ; Kandoth C; Welch J; Ma C; Wendl MC; Payne SH; Fenyö D; Townsend RR; Dipersio JF; Chen F; Ding L Genome Med 2018[]; 10 (ä): ä PMID30053901show ga Background: Although large-scale, next-generation sequencing (NGS) studies of cancers hold promise for enabling precision oncology, challenges remain in integrating NGS with clinically validated biomarkers. Methods: To overcome such challenges, we utilized the Database of Evidence for Precision Oncology (DEPO) to link druggability to genomic, transcriptomic, and proteomic biomarkers. Using a pan-cancer cohort of 6570 tumors, we identified tumors with potentially druggable biomarkers consisting of drug-associated mutations, mRNA expression outliers, and protein/phosphoprotein expression outliers identified by DEPO. Results: Within the pan-cancer cohort of 6570 tumors, we found that 3% are druggable based on FDA-approved drug-mutation interactions in specific cancer types. However, mRNA/phosphoprotein/protein expression outliers and drug repurposing across cancer types suggest potential druggability in up to 16% of tumors. The percentage of potential drug-associated tumors can increase to 48% if we consider preclinical evidence. Further, our analyses showed co-occurring potentially druggable multi-omics alterations in 32% of tumors, indicating a role for individualized combinational therapy, with evidence supporting mTOR/PI3K/ESR1 co-inhibition and BRAF/AKT co-inhibition in 1.6 and 0.8% of tumors, respectively. We experimentally validated a subset of putative druggable mutations in BRAF identified by a protein structure-based computational tool. Finally, analysis of a large-scale drug screening dataset lent further evidence supporting repurposing of drugs across cancer types and the use of expression outliers for inferring druggability. Conclusions: Our results suggest that an integrated analysis platform can nominate multi-omics alterations as biomarkers of druggability and aid ongoing efforts to bring precision oncology to patients. Electronic supplementary material: The online version of this article (10.1186/s13073-018-0564-z) contains supplementary material, which is available to authorized users. äIntegrative omics analyses broaden treatment targets in human cancer (epmc).pdf DeepDyve Pubget Overpricing