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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Integrated computational biology analysis to evaluate target genes for chronic myelogenous leukemia
Yu Zheng1, Yu-Ping Wang2, Hongbao Cao3
1State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Abstract:
Although hundreds of genes have been linked to chronic myelogenous leukemia (CML), many of the results lack reproducibility. In the present study, data across multiple modalities were integrated to evaluate 579 CML candidate genes, including literature‑based CML‑gene relation data, Gene Expression Omnibus RNA expression data and pathway‑based gene‑gene interaction data. The expression data included samples from 76 patients with CML and 73 healthy controls. For each target gene, four metrics were proposed and tested with case/control classification. The effectiveness of the four metrics presented was demonstrated by the high classification accuracy (94.63%; P<2x10‑4). Cross metric analysis suggested nine top candidate genes for CML: Epidermal growth factor receptor, tumor protein p53, catenin β 1, janus kinase 2, tumor necrosis factor, abelson murine leukemia viral oncogene homolog 1, vascular endothelial growth factor A, B‑cell lymphoma 2 and proto‑oncogene tyrosine‑protein kinase. In addition, 145 CML candidate pathways enriched with 485 out of 579 genes were identified (P<8.2x10‑11; q=0.005). In conclusion, weighted genetic networks generated using computational biology may be complementary to biological experiments for the evaluation of known or novel CML target genes.
Insights
This study integrated multiple data types to identify 579 chronic myelogenous leukemia (CML) candidate genes. Nine top genes, including EGFR and TP53, were pinpointed, offering new targets for CML research.
Area of Science:
- Genomics
- Bioinformatics
- Oncology
Background:
- Hundreds of genes are linked to chronic myelogenous leukemia (CML), but reproducibility is a challenge.
- Evaluating candidate genes requires robust methodologies to overcome data variability.
Purpose of the Study:
- To integrate multi-modal data for evaluating 579 CML candidate genes.
- To identify top candidate genes and pathways associated with CML.
- To assess the utility of computational biology in CML gene discovery.
Main Methods:
- Integrated literature-based CML-gene relations, Gene Expression Omnibus RNA expression data, and pathway-based gene-gene interactions.
- Utilized expression data from 76 CML patients and 73 healthy controls.
- Developed and tested four metrics for case/control gene classification achieving high accuracy.
Main Results:
- Achieved 94.63% classification accuracy (P<2x10‑4) in identifying CML-associated genes.
- Identified nine top candidate genes for CML, including EGFR, TP53, JAK2, and VEGF-A.
- Discovered 145 CML candidate pathways enriched with 485 genes (P<8.2x10‑11).
Conclusions:
- Weighted genetic networks from computational biology can complement experimental approaches for CML gene evaluation.
- The study provides a validated list of top CML candidate genes and pathways.
- This integrated approach enhances the reliability of CML gene discovery.
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