Abstract: To analyze the high correlation mutation genes of human pleural mesothelioma by DNA de novo sequencing, DNA was extracted from malignant pleural mesothelioma （MPM） tissues and normal pleural tissues, and a gene library was constructed. The Illumina HiSeqX Ten PE 150 platform was used for sequencing. The sequencing results were compared and annotated with the reference sequence of the human genome database. The sequencing results were filtered, the error rate distribution was checked, and the GC content distribution was checked and analyzed. The average filtering of MPM tissue DNA was 37829946 bp, the error rate was less than 0.12 %, and the GC content accounted for 41.17 %. The average filtering of normal pleural tissue DNA was 39089681 bp, the error rate was less than 0.1 %, and the GC content accounted for 41.7 %. The sequencing quality of both was above Q30 （≥ 80 %）, MPM was 87.43 %, and normal pleura was 88.36 %. The above high-quality sequencing data were compared to the reference genome （GRCh 37 / hg19） by BWA, and the initial alignment sequence was obtained. The coverage and depth of the alignment sequence after repeated labeling were used for statistics. The mutation site was credible when the coverage depth reached 10 X or more. The results showed that 98.59 % of the experimental cases XL14 had a coverage depth of 10 X, and the coverage rate reached 99.83 %. The control case Z5 accounted for 98.50 %, and the coverage rate reached 99.79 %. Gene annotation analysis of the sequence revealed a series of single nucleotide polymorphisms, gene insertion and deletion, gene structure variation, and gene copy number variation. The total number of variation sites was 29277, and the number of possible pathogenic variation sites was 22. The number of pathogenic variation sites was 5, the number of sites with uncertain variation was 3353, and the remaining variation sites were benign. Further enrichment and correlation analysis of mutant genes were carried out to obtain the correlation map and predict the mutation.

Key words: human pleural mesothelioma, de novo sequencing, single nucleotide polymorphism, gene insertion deletion, gene structure variation, gene copy number variation.