Development of computational methods for immune repertoire analysis : from sequence to specificity

dc.contributor.advisorJiang, Ning Jenny
dc.contributor.committeeMemberMarkey, Mia K
dc.contributor.committeeMemberRen, Pengyu
dc.contributor.committeeMemberChen, Keke
dc.creatorHe, Chenfeng
dc.creator.orcid0000-0002-9171-3879
dc.date.accessioned2021-03-23T20:11:31Z
dc.date.available2021-03-23T20:11:31Z
dc.date.created2018-12
dc.date.issued2018-12
dc.date.submittedDecember 2018
dc.date.updated2021-03-23T20:11:31Z
dc.description.abstractThe immune system plays a key role in maintaining human health. Accurately characterizing the immune receptors with immune repertoire sequencing (IRseq) provides an essential way for understanding the adaptive immune system. Towards this goal, we developed a bioinformatics tool, Molecular Identifier Clustering-based IR-Seq (MIDICRS), to quantitatively measure immune repertoire. We have demonstrated MIDCIRS’ accuracy, high coverage and wide dynamic range, which allow us to analyze various types of immune repertoires. Immune repertoire is continuously shaped by encountered antigens; thus, its components reflect an individual’s historical disease status. We applied MIDCIRS to measure the antibody repertoire from malaria-experienced individuals and found unexpected mutable capability of infants adaptive immune system. We also used MIDCIRS to measure Follicular helper T cells (Tfhs) directly obtained from untreated HIV patients’ lymph nodes and found (1) evidence for intact antigen-driven clonal expansion of Tfh cells and (2) selective utilization of specific complementarity-determining region 3 (CDR3) motifs during chronic HIV infection. Both studies demonstrated MIDCIRS functionality and versatility for studying antigen driven immune response. Bridging the gap between immune receptor sequences and their biological function (i.e. antigen specificity) is attractive and useful for directly measuring immune repertoire changes with respect to pathogen infection. Using experimentally validated CD8+ TCR sequences with their antigen specificity, we developed a computational tool, Linear programming based Motif Pick and Enrichment analysis for Tcrs (LiMPETs), to find significant motifs within the TCR CDR3 region for determining antigen specificity. We demonstrated LiMPETs’ advantages by comparing with existing tools on both public and in-house data
dc.description.departmentBiomedical Engineering
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/2152/85071
dc.identifier.urihttp://dx.doi.org/10.26153/tsw/12041
dc.language.isoen
dc.subjectImmune repertoire
dc.subjectAntigen specificity
dc.subjectImmune clonal expansion
dc.titleDevelopment of computational methods for immune repertoire analysis : from sequence to specificity
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentBiomedical Engineering
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorThe University of Texas at Austin
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
HE-DISSERTATION-2018.pdf
Size:
5.55 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
PROQUEST_LICENSE.txt
Size:
4.45 KB
Format:
Plain Text
Description:
No Thumbnail Available
Name:
LICENSE.txt
Size:
1.84 KB
Format:
Plain Text
Description: