Characterization of the human transcriptome diversity and its implication in identifying cancer-specific regions of transcripts

dc.contributor.authorDas, Urmi
dc.contributor.examiningcommitteeDodd, Janice (Physiology & Pathophysiology)en_US
dc.contributor.examiningcommitteeMishra, Suresh (Physiology & Pathophysiology)en_US
dc.contributor.examiningcommitteeLeygue, Etienne (Biochemistry & Medical Genetics)en_US
dc.contributor.examiningcommitteeAlfonzo, Juan D. (The Ohio State University)en_US
dc.contributor.supervisorXie, Jiuyong (Physiology & Pathophysiology)en_US
dc.date.accessioned2021-11-29T20:02:32Z
dc.date.available2021-11-29T20:02:32Z
dc.date.copyright2021-11-15
dc.date.issued2021-11-15en_US
dc.date.submitted2021-11-15T18:59:58Zen_US
dc.degree.disciplinePhysiology and Pathophysiologyen_US
dc.degree.levelDoctor of Philosophy (Ph.D.)en_US
dc.description.abstractThe emergence of exons and introns in eukaryotes has increased the potential of gene products and their functional diversity to a greater extent than in prokaryotes. In humans, the transcriptome has the highest percentage of multi-exon genes that contain at least one alternatively spliced exon. At the exon level, however, it is the constitutive exons that have been observed more often in gene transcripts. This trend has been shifting with the increasing numbers of alternative exons per gene. Here, we estimate the differentially used exons (DEXs) of human RNA transcripts at a saturation level among 1,540 pairs of 56 nominally normal tissues with DEXs comprising at least 72% of the human exome. Our result has shifted the paradigm of exon usage from mainly constitutive to differentially used exons in the human transcriptome, suggesting a more diverse and dynamic transcript repertoire of the human transcriptome than previously reported. We used this comprehensive catalogue of DEXs of the normal transcriptome as background for further analysis against the cancer transcriptomes. We demonstrated that 99% of the aberrantly processed exons of adenocarcinoma also exist in the normal transcriptome blueprint of DEXs showing similar processing pattern as normal in other non-cancerous tissues. A small group of authentic ‘cancer-specific’ exons that were found only in cancer patients harboring specific gene mutations, were not found in any of the normal tissues. Thus, our results also reveal the ectopic expression of nearly all ‘cancer-specific’ exons of adenocarcinoma compared to the corresponding normal tissue of origin. This will help selection for authentic ‘cancer-specific’ target exons for diagnostic or therapeutic purposes.en_US
dc.description.noteFebruary 2022en_US
dc.identifier.urihttp://hdl.handle.net/1993/36123
dc.rightsopen accessen_US
dc.subjectTranscriptomeen_US
dc.subjectAlternative splicingen_US
dc.subjectConstitutive exonen_US
dc.subjectDiversityen_US
dc.subjectAdenocarcinomaen_US
dc.subjectSpecificityen_US
dc.titleCharacterization of the human transcriptome diversity and its implication in identifying cancer-specific regions of transcriptsen_US
dc.typedoctoral thesisen_US
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