摘要:
Genomics, transcriptomics, and proteomics are fundamental blocks that shaped modern biology. High throughput and large-scale techniques, such as next-generation sequencing (NGS) and mass spectrometry (MS), have been widely used in the life sciences. Due to the complexity of these data, the analysis needs to be done by sophisticated bioinfor-matic methods. During my doctorate research, I developed new computational methods and applied new strategies to advance the research in genomics, transcriptomics, and proteomics. NGS has brought tremendous and numerous changes to genomic research by providing higher sensitivity, sequencing depth, and throughput compared with traditional sequenc-ing methods, such as Sanger sequencing, qPCR, and microarrays. Benefiting from the advantages of NGS technology, RNA-seq has been widely used for the qualitative and quantitative analysis of genome wide changes in gene expression. Chromatin immuno-precipitation sequencing (ChIP-seq) as another popular application of NGS provides an efficient way to analyze the interaction between proteins and DNA. During my doctoral studies, I used these techniques to uncover the mechanisms behind the hybrid incompat-ibility between Drosophila melanogaster and D. simulans. The loss of HMR in D. melanogaster leads to mitotic defects, increased transcription of transposable elements, and deregulated heterochromatic genes. Through the genome-wide analysis of HMR's localization by ChIP-seq, I found that genomic insulator sites bound by HMR can be grouped into two clusters. One set is composed of gypsy insula-tors, whereas the other is bordered by HP1a-bound areas of active genes. In Hmr mu-tant flies, the transcription of genes belonging to the latter group is severely disrupted in larval tissue and ovaries. These findings showed a novel connection between HMR and insulator proteins, indicating a possible role for genome organization in species devel-opment. Beyond the study of particular genes, and RNA trans