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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biomed+Semantics
2017 ; 8
(1
): 40
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Towards precision medicine: discovering novel gynecological cancer biomarkers and
pathways using linked data
#MMPMID28927463
Jha A
; Khan Y
; Mehdi M
; Karim MR
; Mehmood Q
; Zappa A
; Rebholz-Schuhmann D
; Sahay R
J Biomed Semantics
2017[Sep]; 8
(1
): 40
PMID28927463
show ga
BACKGROUND: Next Generation Sequencing (NGS) is playing a key role in therapeutic
decision making for the cancer prognosis and treatment. The NGS technologies are
producing a massive amount of sequencing datasets. Often, these datasets are
published from the isolated and different sequencing facilities. Consequently,
the process of sharing and aggregating multisite sequencing datasets are thwarted
by issues such as the need to discover relevant data from different sources,
built scalable repositories, the automation of data linkage, the volume of the
data, efficient querying mechanism, and information rich intuitive visualisation.
RESULTS: We present an approach to link and query different sequencing datasets
(TCGA, COSMIC, REACTOME, KEGG and GO) to indicate risks for four cancer types -
Ovarian Serous Cystadenocarcinoma (OV), Uterine Corpus Endometrial Carcinoma
(UCEC), Uterine Carcinosarcoma (UCS), Cervical Squamous Cell Carcinoma and
Endocervical Adenocarcinoma (CESC) - covering the 16 healthy tissue-specific
genes from Illumina Human Body Map 2.0. The differentially expressed genes from
Illumina Human Body Map 2.0 are analysed together with the gene expressions
reported in COSMIC and TCGA repositories leading to the discover of potential
biomarkers for a tissue-specific cancer. CONCLUSION: We analyse the tissue
expression of genes, copy number variation (CNV), somatic mutation, and promoter
methylation to identify associated pathways and find novel biomarkers. We
discovered twenty (20) mutated genes and three (3) potential pathways causing
promoter changes in different gynaecological cancer types. We propose a
data-interlinked platform called BIOOPENER that glues together heterogeneous
cancer and biomedical repositories. The key approach is to find correspondences
(or data links) among genetic, cellular and molecular features across isolated
cancer datasets giving insight into cancer progression from normal to diseased
tissues. The proposed BIOOPENER platform enriches mutations by filling in missing
links from TCGA, COSMIC, REACTOME, KEGG and GO datasets and provides an
interlinking mechanism to understand cancer progression from normal to diseased
tissues with pathway components, which in turn helped to map mutations,
associated phenotypes, pathways, and mechanism.