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You searched for +publisher:"Vanderbilt University" +contributor:("John Anthony Capra"). Showing records 1 – 3 of 3 total matches.

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Vanderbilt University

1. Herring, Charles Albert. Cell Fate Relationships Mapped by p-Creode Trajectory Analysis of Single-cell Data.

Degree: PhD, Chemical and Physical Biology, 2018, Vanderbilt University

Modern single-cell technologies allow multiplexed sampling of cellular states within a tissue. However, computational tools that can infer developmental cell-state transitions reproducibly from such single-cell data are lacking. Here, introduced is p-Creode, an unsupervised algorithm that produces multi-branching graphs from single-cell data, compares graphs with differing topologies, and infers a statistically robust hierarchy of cell-state transitions that define developmental trajectories. p-Creode is applied to mass cytometry, multiplex immunofluorescence, and single-cell RNA-seq data. As a test case, we validate cell-state-transition trajectories predicted by p-Creode for intestinal tuft cells, a rare, chemosensory cell type. We clarify that tuft cells are specified outside of the Atoh1-dependent secretory lineage in the small intestine. However, p-Creode also predicts, and we confirm, that tuft cells arise from an alternative, Atoh1-driven developmental program in the colon. These studies introduce p-Creode as a reliable method for analyzing large datasets that depict branching transition trajectories. Advisors/Committee Members: John Anthony Capra (committee member), Erin Rericha (committee member), Ken Lau (committee member), Gregor Neuert (committee member), Vito Quaranta (Committee Chair).

Subjects/Keywords: differentiation hierarchies; trajectories; pseudo-time analysis; single-cell RNA-seq; intestine and colon; mass cytometry; graph theory; tuft cells; cell-state transitions; single-cell biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Herring, C. A. (2018). Cell Fate Relationships Mapped by p-Creode Trajectory Analysis of Single-cell Data. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11790

Chicago Manual of Style (16th Edition):

Herring, Charles Albert. “Cell Fate Relationships Mapped by p-Creode Trajectory Analysis of Single-cell Data.” 2018. Doctoral Dissertation, Vanderbilt University. Accessed April 10, 2021. http://hdl.handle.net/1803/11790.

MLA Handbook (7th Edition):

Herring, Charles Albert. “Cell Fate Relationships Mapped by p-Creode Trajectory Analysis of Single-cell Data.” 2018. Web. 10 Apr 2021.

Vancouver:

Herring CA. Cell Fate Relationships Mapped by p-Creode Trajectory Analysis of Single-cell Data. [Internet] [Doctoral dissertation]. Vanderbilt University; 2018. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1803/11790.

Council of Science Editors:

Herring CA. Cell Fate Relationships Mapped by p-Creode Trajectory Analysis of Single-cell Data. [Doctoral Dissertation]. Vanderbilt University; 2018. Available from: http://hdl.handle.net/1803/11790


Vanderbilt University

2. Fish, Alexandra Elizabeth. Leveraging gene expression and local ancestry to investigate regulatory epistasis in humans.

Degree: PhD, Human Genetics, 2017, Vanderbilt University

Epistasis is a phenomenon wherein the effect of a genetic variant on a phenotype is dependent on the genomic context. Better understanding epistastic relationships between variants, often termed interactions, can shed light on novel genomic loci associated with complex disease, which may improve our understanding of the underlying biological mechanisms. Additionally, capturing epistastic effects in models of disease risk may help improve predictions of at-risk populations, or the prediction of a variant’s deleteriousness in precision medicine initiatives. However, the study of epistasis faces unique methodological challenges, and consequently, evidence for regulatory epistasis remains elusive in humans. In this work, I address two major challenges within the field of regulatory epistasis: the development of statistical best practices, and the investigation of epistasis within haplotypes. In Chapter 2, I illustrate that traditional quality control procedures are insufficient to correct for confounding in studies of epistasis, and develop a set of additional guidelines for future studies. Once these were applied, I found little evidence for epistasis between common, unlinked variants influencing gene expression levels. In Chapter 3, I leverage unique properties of admixed populations to investigate epistasis within ancestral haplotypes disrupted by ancestry-specific recombination events. I find several examples of epistasis with plausible biological support, which serve as a proof of principle for the utility of this approach. Overall, these findings indicate that regulatory epistasis likely has small effects, occurs within haplotypes, or occurs between distant genomic regions; we recommend future studies of epistasis focus on these possibilities. Advisors/Committee Members: William Scott Bush (committee member), John Anthony Capra (committee member), Melinda Aldrich (committee member), Joseph Lee Rodgers (committee member), Douglas P. Mortlock (Committee Chair).

Subjects/Keywords: epistasis; gene expression; admixed populations; eQTL; PheWAS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Fish, A. E. (2017). Leveraging gene expression and local ancestry to investigate regulatory epistasis in humans. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11250

Chicago Manual of Style (16th Edition):

Fish, Alexandra Elizabeth. “Leveraging gene expression and local ancestry to investigate regulatory epistasis in humans.” 2017. Doctoral Dissertation, Vanderbilt University. Accessed April 10, 2021. http://hdl.handle.net/1803/11250.

MLA Handbook (7th Edition):

Fish, Alexandra Elizabeth. “Leveraging gene expression and local ancestry to investigate regulatory epistasis in humans.” 2017. Web. 10 Apr 2021.

Vancouver:

Fish AE. Leveraging gene expression and local ancestry to investigate regulatory epistasis in humans. [Internet] [Doctoral dissertation]. Vanderbilt University; 2017. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1803/11250.

Council of Science Editors:

Fish AE. Leveraging gene expression and local ancestry to investigate regulatory epistasis in humans. [Doctoral Dissertation]. Vanderbilt University; 2017. Available from: http://hdl.handle.net/1803/11250


Vanderbilt University

3. Strnad, Jessica Ann. Sequence, Structure, and Function Relationships of Human Antibodies.

Degree: PhD, Microbiology and Immunology, 2018, Vanderbilt University

The human adaptive immune system is mediated in part by B cells, which produce antibodies to protect the body from infection. Antibodies are protein molecules responsible for recognizing and binding pathogenic targets (i.e., antigens) to mediate effective neutralization of the microorganism. In recent years, emerging technologies such as next generation sequencing and computational structure prediction have had a substantial impact on studies of human antibodies. These technologies have improved our understanding of antibody sequence, structure and function relationships. The development of a broadly protective anti-influenza antibody response following vaccination was tracked over time using next generation sequencing. Knowledge-based restraints calculated from analysis of conserved structural motifs in antigen-binding antibody protein loops improved the accuracy of antibody structural predictions using the Rosetta software suite for macromolecular modeling. Combining these sequencing techniques with structure prediction allowed for the development of a novel method for structure-based discovery of functional antibodies from human donors. Advisors/Committee Members: James W. Thomas, II (committee member), Andrew J. Link (committee member), James E. Crowe, Jr. (committee member), Jens Meiler (committee member), John Anthony Capra (committee member), Jonathan M. Irish (committee member), Mark Denison (Committee Chair).

Subjects/Keywords: B cell; structural modeling; next generation sequencing; antibody repertoire; influenza; Rosetta

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Strnad, J. A. (2018). Sequence, Structure, and Function Relationships of Human Antibodies. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14560

Chicago Manual of Style (16th Edition):

Strnad, Jessica Ann. “Sequence, Structure, and Function Relationships of Human Antibodies.” 2018. Doctoral Dissertation, Vanderbilt University. Accessed April 10, 2021. http://hdl.handle.net/1803/14560.

MLA Handbook (7th Edition):

Strnad, Jessica Ann. “Sequence, Structure, and Function Relationships of Human Antibodies.” 2018. Web. 10 Apr 2021.

Vancouver:

Strnad JA. Sequence, Structure, and Function Relationships of Human Antibodies. [Internet] [Doctoral dissertation]. Vanderbilt University; 2018. [cited 2021 Apr 10]. Available from: http://hdl.handle.net/1803/14560.

Council of Science Editors:

Strnad JA. Sequence, Structure, and Function Relationships of Human Antibodies. [Doctoral Dissertation]. Vanderbilt University; 2018. Available from: http://hdl.handle.net/1803/14560

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