Proteomics

Dataset Information

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Computational analysis of cholangiocarcinoma phosphoproteomes identifies patient-specific drug targets


ABSTRACT: We used mass-spectrometry based phosphoproteomics and computational methods to identify patient-specific drug targets in primary CCA and CCA-derived cell lines. We analyzed 13 primary CCA with matched background tissue and 8 different cell lines leading to the identification and quantification of >13,000 phosphorylation sites. Application of the Drug Ranking Using Machine Learning (DRUML) algorithm identified inhibitors of HDAC and PI3K pathway members as highly ranking in primary CCA relative to background. The accuracy of drug rankings based on predicted responses was confirmed using cell line models of CCA. Together, our study uncovers frequently overactive biochemical pathways in primary CCA and provides a proof-of-concept of the use of machine learning for ranking drugs based on efficacy within individual patient tumors.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cholangiocarcinoma Cell, Epithelial Cell

DISEASE(S): Cholangiocarcinoma

SUBMITTER: Vinothini Rajeeve  

LAB HEAD: Professor Pedro R Cutillas

PROVIDER: PXD027329 | Pride | 2023-03-11

REPOSITORIES: pride

Dataset's files

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B10a.raw Raw
B10a.raw.-1.mgf Mgf
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B10b.raw.-1.mgf Mgf
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Publications

Computational Analysis of Cholangiocarcinoma Phosphoproteomes Identifies Patient-Specific Drug Targets.

Khorsandi Shirin Elizabeth SE   Dokal Arran D AD   Rajeeve Vinothini V   Britton David J DJ   Illingworth Megan S MS   Heaton Nigel N   Cutillas Pedro R PR  

Cancer research 20210922 22


Cholangiocarcinoma is a form of hepatobiliary cancer with an abysmal prognosis. Despite advances in our understanding of cholangiocarcinoma pathophysiology and its genomic landscape, targeted therapies have not yet made a significant impact on its clinical management. The low response rates of targeted therapies in cholangiocarcinoma suggest that patient heterogeneity contributes to poor clinical outcome. Here we used mass spectrometry-based phosphoproteomics and computational methods to identif  ...[more]

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