PreMedKB: an integrated precision medicine knowledgebase for interpreting relationships between diseases, genes, variants and drugs

Yu, Ying; Wang, Yunjin; Xia, Zhaojie; Zhang, Xiangyu; Jin, Kailiang; Yang, Jingcheng; Ren, Luyao; Zhou, Zheng; Dong, Yu; Qing, Tao; Zhang, Chengdong; Li, Jin; Zheng, Yuanting; Guo, Li; Shi, Leming

doi:10.1093/nar/gky1042

Cited by 39 publications

(36 citation statements)

References 44 publications

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“…Tools similar to CDGnet include PreMedKB 47 and Drug Gene Interaction Network. PreMedKB (http://www.fudan-pgx.org/premedkb/) is an integrated precision medicine knowledgebase for interpreting relationships between diseases, genes, variants, and drugs.…”

Section: Discussionmentioning

confidence: 99%

An evidence-based network approach to recommending targeted cancer therapies

Kancherla

Rao

Bhuvaneshwar

et al. 2019

Preprint

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In this work, we introduce CDGnet, an evidence-based network approach for recommending targeted cancer therapies, available as a user-friendly informatics tool. Our approach can be used to expand the range of options of targeted therapies for cancer patients who undergo molecular profiling. It considers biological pathway information specifically by looking at downstream targets of oncogenes and is personalized for individual patients via the user-inputted molecular alterations and cancer type. CDGnet integrates disparate sources of knowledge and provides results in a number of easily-accessible and usable forms, while separating targeted cancer therapies into categories in an evidence-based manner.

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Section: Discussionmentioning

confidence: 99%

An evidence-based network approach to recommending targeted cancer therapies

Kancherla

Rao

Bhuvaneshwar

et al. 2019

Preprint

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“…Precision medicine. Precision oncology focuses on matching the most effective treatment based on the 'omics' profile of each individual or population 70,71 . The CGI (https://www.cancergenomeinterpreter.org/home) flags genomic biomarkers of drug response with different levels of clinical relevance 38 .…”

Section: Methodsmentioning

confidence: 99%

“…Long et al 74,75 , Cai et al 76 , and Michailidou et al 77 , performed genome-wide association studies identifying germline variations related to BC development. PreMedKB (http://www.fudan-pgx.org/premedkb/index.html#/home) is a bioinformatics tool that facilitates the interpretation of the clinical meaning of a patient's genetic variants 71 . PharmGKB (https://www.pharmgkb.org/) collected complete guidelines for application of pharmacogenomics in clinical practice, according to several consortiums worldwide [43][44][45][46] .…”

Section: Methodsmentioning

confidence: 99%

“…www.nature.com/scientificreports www.nature.com/scientificreports/ Precision medicine. Precision oncology focuses on matching the most effective and safe treatment based on the 'omics' profile of each individual or population 70,71 . However, the identification of driver mutational events remains the biggest challenge 72 .…”

Section: Oncoomics Approaches To Reveal Essential Genes In Bcmentioning

confidence: 99%

“…Long et al 74,75 , Cai et al 76 , Michailidou et al 77 , and the Breast Cancer Association Consortium performed genome-wide association www.nature.com/scientificreports www.nature.com/scientificreports/ studies identifying 172 germline variations related to BC development ( Supplementary Table S34). The Precision Medicine Knowledgebase (PreMedKB) detailed a compendium of 2791 germline variants in 7 OncoOmics BC essential genes ( Supplementary Table S35) 71 . PharmGKB enriched clinical guidelines with 59 well-known clinical annotations related to 29 OncoOmics BC essential genes ( Supplementary Table S36) 42,78,79 .…”

Section: Oncoomics Approaches To Reveal Essential Genes In Bcmentioning

confidence: 99%

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OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine

López‐Cortés

Paz‐y‐Miño

Guerrero

et al. 2020

Sci Rep

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Breast cancer (Bc) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes . RAC1, AKT1, CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, BCL2, CTNNB1, EGFR, CDK2, GRB2, MED1 and GATA3 were essential genes in at least three oncoomics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.Breast cancer (BC) is a complex and heterogeneous disease characterized by an intricate interplay between different biological aspects such as ethnicity, genomic alterations, gene expression deregulation, hormone disruption, signaling pathway alterations, hypoxia, and environmental determinants 1,2 . Over the last years, prevention, treatment and survival strategies have evolved favorably; however, there are BC profiles that remain incurable 3 .

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