Establish Reporting Format of Gene Related Rare-Diseases by Exome Sequencing in the Clinical Medical Laboratory
2016 IEEE 16th International Conference on Bioinformatics and Bioengineering (BIBE) (2016)
Oct. 31, 2016 to Nov. 2, 2016
DOI Bookmark: http://doi.ieeecomputersociety.org/10.1109/BIBE.2016.66
Background: Next-generation sequencing (NGS) testing has two analytical processes, wet bench and bioinformatics process. Exome sequencing covers about 20000 human protein-coding gene sequences. Since these sequences are only 2% of human genome, but can predict 85% of human gene related diseases, whole exome sequencing is the most cost-effective test to diagnose unknown genetic diseases. Methods: Analysis methods developed by the Department of Laboratory Medicine of China Medical University Hospital (CMUH) with compliance of the molecular pathology checklists of the College of American Pathologists (CAP). Results: We developed the exome sequencing analysis workflow. First, single nucleotide polymorphism, SNP known with a minor allele frequency (MAF) >1%, was excluded. Second, variants other than SNP detected by NGS are submitted to the ClinVar database, which divided the relationships between variants and clinical significances into five categories: benign, likely benign, uncertain, likely pathogenic, and pathogenic. Third, all pathogenic variants, also confirmed by Sanger sequencing, might be current clinical relevance or incidental findings. Fourth, uncertain clinical significance variants with a MAF 30% were underwent further analysis by three pathogenicity predictions software: SIFT, PolyPhen, and CADD_PHRED. The final report from of exome sequencing contain sections of summary, clinical relevance (pathogenic), incidental finding (pathogenic), benign / likely benign, GWAS-related diseases, uncertain significance (including the results of three pathogenic software analysis), and the performance of the NGS platform. Conclusions: we demonstrated a reasonable working flow and a clinical practicable reporting format of exome sequencing by NGS.
Sequential analysis, Diseases, Hospitals, Bioinformatics, Medical diagnostic imaging, Genomics
C. Ho, H. Huang, C. Yang, Y. Chang, C. Lin and J. Chang, "Establish Reporting Format of Gene Related Rare-Diseases by Exome Sequencing in the Clinical Medical Laboratory," 2016 IEEE 16th International Conference on Bioinformatics and Bioengineering (BIBE), Taichung, Taiwan, 2016, pp. 390-392.