Browsing by Author "Chen, Yujie"

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    Computational Analysis of Cancer Genomic Evolution and Human Endogenous Double-stranded RNA
    (2023-10-10) Chen, Yujie; Kimmel, Marek
    The development of next generation sequencing (NGS) technologies has allowed rapid and cost-effective sequencing of large amounts of DNA or RNA, enabling systematic analysis of biological and pathological processes. Interpretation of genomic and transcriptomic data became crucial in both research and clinical settings, particularly for investigating complex human diseases. This thesis employed various computational analysis methods in three projects that utilized different types of NGS data: (1) Constructing genomic trajectory for the progression process of multiple hematopoietic malignancies using panel sequencing and karyotype data; (2) Mathematical modeling of the mutation accumulation history in bladder cancer on a whole-organ level; and (3) Identifying endogenous immunogenetic double-stranded RNA species by classic bioinformatic analysis of RNA-seq data. The research conducted in this thesis revealed genomic evolution dynamics in cancer development providing important reference for cancer progression monitoring and intervention, and shed light on RNA therapeutic targets in autoimmune diseases.
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    Genomic trajectory in leukemogenesis of myeloproliferative neoplasms: a case report
    (BioMed Central, 2021) Chen, Yujie; Talukder, Rafee; Merritt, Brian Y.; King, Katherine Y.; Kimmel, Marek; Rivero, Gustavo; Sosa, Romina
    We report a patient with Essential Thrombocythemia (ET), subsequently diagnosed with concurrent myeloid and lymphoid leukemia. Generally, the molecular mechanisms underlying leukemic transformation of Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are poorly understood. Risk of transformation to acute myelogenous leukemia (AML) is low; transformation to both AML and acute lymphoblastic leukemia (ALL) is extremely low. Genetic defects, including allele burden, order of mutation acquisition, clonal heterogeneity and epigenetic mechanisms are important contributors to disease acceleration.
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    The origin of bladder cancer from mucosal field effects
    (Cell Press, 2022) Bondaruk, Jolanta; Jaksik, Roman; Wang, Ziqiao; Cogdell, David; Lee, Sangkyou; Chen, Yujie; Dinh, Khanh Ngoc; Majewski, Tadeusz; Zhang, Li; Cao, Shaolong; Tian, Feng; Yao, Hui; Kuś, Paweł; Chen, Huiqin; Weinstein, John N.; Navai, Neema; Dinney, Colin; Gao, Jianjun; Theodorescu, Dan; Logothetis, Christopher; Guo, Charles C.; Wang, Wenyi; McConkey, David; Wei, Peng; Kimmel, Marek; Czerniak, Bogdan
    Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysregulated pathways, involving immunity, differentiation, and transformation, as initiators of carcinogenesis. Dysregulation of interleukins signified the involvement of inflammation in the incipient phases of the process. An aberrant methylation/expression of multiple HOX genes signified dysregulation of the differentiation program. We identified three types of mutations based on their geographic distribution. The most common were mutations restricted to individual mucosal samples that targeted uroprogenitor cells. Two types of mutations were associated with clonal expansion and involved large areas of mucosa. The α mutations occurred at low frequencies while the β mutations increased in frequency with disease progression. Modeling revealed that bladder carcinogenesis spans 10–15 years and can be divided into dormant and progressive phases. The progressive phase lasted 1-2 years and was driven by β mutations.