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Development and Application of Advanced Methodologies for Genome Dissection

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Abstract

Next-generation sequencing (NGS) technologies have become an established and affordable framework for generating genomic information about living organisms. NGS data usually are bulky, complicated, and imperfect, which makes processing and analyzing NGS data challenging. Although many methods for NGS data analysis have emerged in the past years, the continuing development of advanced algorithms and tools is desperately wanted to tackle the dramatically growing data. Moreover, there are always misunderstandings between the end user and the developer. Proper, well-developed, explicit pipelines and many real data tests could bridge the gap between data generation and hypothesis testing.The first chapter proposed an advanced algorithm IIIandMe, which infers chromosome- scale haplotypes using genomic data of single gametes. Theoretically, only three gametes are sufficient in our hypothesis, and then the simulation of maize data and real data of citrus were tested as shreds of evidence. In the second chapter, the EM algorithm for probit and logistic regressions was introduced in a language style that is easy to understand by biologists to analyze binary traits in biology and agriculture and thus promotes wide applications of the generalized linear model (GLM) and generalized linear mixed model (GLMM) to biological problems. The third chapter performed whole genome phylogenomic analyses to decipher the phylogenetic relationships and diversification within the Punica genus. Our phylogenomic pipeline has empowered the use of low-coverage and fragmented whole genomes, providing productive perspectives for future research of other model groups. The fourth chapter provided a general mechanism for establishing circadian rhythm heterogeneity during development and disease progression governed by chromatin structure. We report that knockout of the lineage-specifying Hnf4a gene in mouse liver causes associated reductions in the genome-wide distribution of core clock component BMAL1 and accessible chromatin marks (H3K4me1 and H3K27ac), underlying circadian control of peripheral metabolism and its observed perturbation in human diseases.

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This item is under embargo until January 26, 2025.