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Aviv Regev. Dixit, Atray (Atray Chitanya) Harvard--MIT Program in Health Sciences and Technology. Harvard University--MIT Division of Health Sciences and Technology 2018-09-17T15:49:03Z 2018-09-17T15:49:03Z 2018 2018 http://hdl.handle.net/1721.1/117897 1051214946 Thesis: Ph. D. in Medical Engineering and Medical Physics, Harvard-MIT Program in Health Sciences and Technology, 2018. Cataloged from PDF version of thesis. Includes bibliographical references. Complex hierarchical structures are a hallmark of life. Within multicellular organisms, the building blocks of these structures are cells; within cells, they are genes. The interdependence of these building blocks is difficult to measure but is integral to the biological processes of health and disease, which emerge from the dynamism of thousands of interacting genes. This cooperativity manifests in particular mutations which accumulate over the course of cancer progression, gender-specific medical conditions, and transcription factor cocktails used to reprogram differentiated cells into stem cells. However, it is experimentally intractable to test the significance of perturbing every unique combination of genes. Instead, we explore gross features of this interaction space to determine how prevalent these synergies are. We take a top-down approach, creating new methods to measure the effects of removing genes from the full set. In the first, we develop a method to measure the transcriptional response to genetic perturbations across hundreds of thousands of cells revealing opposing classes of transcription factors regulating the immune response of dendritic cells. In the second, we create a method to measure how millions of combinations of genetic perturbations impact the growth rate of cancer cell lines. by Atray Dixit. Ph.D. in Medical Engineering and Medical Physics 152 pages eng Massachusetts Institute of Technology MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 Harvard--MIT Program in Health Sciences and Technology. Methods for bounding genetic nonlinearities Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="0f87423f-c1b7-4e5f-91d8-4248c2b6a35c"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Methods for bounding genetic nonlinearities</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2018</PublicationDate> <Authors> <Author> <DisplayName>Dixit, Atray (Atray Chitanya)</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Harvard--MIT Program in Health Sciences and Technology.</Keyword> <Abstract>Complex hierarchical structures are a hallmark of life. Within multicellular organisms, the building blocks of these structures are cells; within cells, they are genes. The interdependence of these building blocks is difficult to measure but is integral to the biological processes of health and disease, which emerge from the dynamism of thousands of interacting genes. This cooperativity manifests in particular mutations which accumulate over the course of cancer progression, gender-specific medical conditions, and transcription factor cocktails used to reprogram differentiated cells into stem cells. However, it is experimentally intractable to test the significance of perturbing every unique combination of genes. Instead, we explore gross features of this interaction space to determine how prevalent these synergies are. We take a top-down approach, creating new methods to measure the effects of removing genes from the full set. In the first, we develop a method to measure the transcriptional response to genetic perturbations across hundreds of thousands of cells revealing opposing classes of transcription factors regulating the immune response of dendritic cells. In the second, we create a method to measure how millions of combinations of genetic perturbations impact the growth rate of cancer cell lines.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>