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A Novel Prioritization Method in Identifying Recurrent Venous Thromboembolism-Related Genes.

ABSTRACT: Identifying the genes involved in venous thromboembolism (VTE) recurrence is important not only for understanding the pathogenesis but also for discovering the therapeutic targets. We proposed a novel prioritization method called Function-Interaction-Pearson (FIP) by creating gene-disease similarity scores to prioritize candidate genes underling VTE. The scores were calculated by integrating and optimizing three types of resources including gene expression, gene ontology and protein-protein interaction. As a result, 124 out of top 200 prioritized candidate genes had been confirmed in literature, among which there were 34 antithrombotic drug targets. Compared with two well-known gene prioritization tools Endeavour and ToppNet, FIP was shown to have better performance. The approach provides a valuable alternative for drug targets discovery and disease therapy.

SUBMITTER: Jiang J

PROVIDER: S-EPMC4822849 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Novel Prioritization Method in Identifying Recurrent Venous Thromboembolism-Related Genes.

Jiang Jing J Li Wan W Liang Binhua B Xie Ruiqiang R Chen Binbin B Huang Hao H Li Yiran Y He Yuehan Y Lv Junjie J He Weiming W Chen Lina L

PloS one 20160406 4

Identifying the genes involved in venous thromboembolism (VTE) recurrence is important not only for understanding the pathogenesis but also for discovering the therapeutic targets. We proposed a novel prioritization method called Function-Interaction-Pearson (FIP) by creating gene-disease similarity scores to prioritize candidate genes underling VTE. The scores were calculated by integrating and optimizing three types of resources including gene expression, gene ontology and protein-protein inte ...[more]

PMID: 27050193

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Project description:ImportanceThe size of the risk of recurrent venous thromboembolism (VTE) after surgery in patients with a history of VTE is not well known.ObjectivesTo estimate the risk of and to identify the factors associated with recurrent VTE in patients undergoing surgery who have a history of VTE.Design, setting, and participantsThis population-based, follow-up cohort study includes patients with VTE who participated in the Multiple Environment and Genetic Assessment (MEGA) study. Original data were collected from March 1999 to April 2010. Data analysis began in June 1999 and ended in April 2010.ExposuresSurgery following a first VTE.Main outcomes and measurementsKaplan-Meier analyses were used to estimate cumulative incidences of recurrent VTE. Cox regression with a time-dependent covariate (surgery) was used to calculate the hazard ratio (HR) for developing recurrent VTE after surgery compared with no surgery.ResultsOverall, 3741 patients (mean [SD] age, 48.4 [12.8] years; 2020 [54.0%] women) with a history of VTE were included in the analysis, amounting to 18 899 person-years, with a median (interquartile range) follow-up of 5.7 (3.0-7.2) years. Of the 3741 patients, 580 (15.5%) underwent surgery and 601 (16.1%) developed a recurrent thrombotic event. The 1-month cumulative incidence of recurrent VTE for all surgery types was 2.1% (95% CI, 1.2%-3.6%), which increased to 3.3% (95% CI, 2.1%-5.1%) at 3 months and 4.6% (95% CI, 3.1%-6.6%) at 6 months. At 6 months, risk of recurrent VTE ranged from 2.3% to 9.3%, depending on surgery type. In addition to surgery type, factor V Leiden mutation (HR, 3.4; 95% CI, 1.6-7.4) and male sex (HR, 2.7; 95% CI, 1.3-5.8) were associated with increased risk of recurrent VTE.Conclusions and relevanceSurgery was associated with an increased risk of recurrent VTE in patients with a history of VTE; risk remained high for up to 6 months after the procedure. This study suggests that high-risk individuals may be identified based on surgery type, sex, and the presence of factor V Leiden mutation. These findings stress the need for revision of the current thromboprophylactic approach to prevent recurrence in these patients.

Dataset Information

A Novel Prioritization Method in Identifying Recurrent Venous Thromboembolism-Related Genes.

Publications

A Novel Prioritization Method in Identifying Recurrent Venous Thromboembolism-Related Genes.

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