Thesis
Structure-aware tools for the development of therapeutic antibodies from natural immunoglobulins
- Abstract:
- In this thesis, we establish the foundations for structure-based antibody drug discovery from natural immunoglobulin sequences. This is achieved through two novel software packages: ‘Repertoire Structural Profiling’ (RSP), as a means of generating structurally-diverse virtual screening libraries, and the ‘Therapeutic Antibody Profiler’ (TAP), for rapid structure-aware developability assessment of candidates in early-stage antibody drug discovery. Our approaches are orthogonal to existing work in these fields and yield new insights into the diversity of the adaptive immune system and the physicochemical characteristics of therapeutic antibodies. We also describe a new database (Thera-SAbDab), which provides the increased therapeutic antibody sequence and structural data necessary to benchmark RSP and TAP, and to facilitate future investigations in the area. Finally, we report our work in the COVID-19 response effort, which, through a novel database of thousands of coronavirus antibody-binders (CoV-AbDab), has already contributed functional annotations to SARS-CoV-2 immune response repertoires.
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(Preview, Dissemination version, Version of record, pdf, 100.7MB, Terms of use)
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Authors
Contributors
+ Deane, C
- Institution:
- University of Oxford
- Division:
- MPLS
- Department:
- Statistics
- Research group:
- Oxford Protein Informatics Group
- Oxford college:
- St Anne's College
- Role:
- Supervisor
- ORCID:
- 0000-0003-1388-2252
+ Marsden, B
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDORMS
- Research group:
- Research Informatics Group
- Role:
- Examiner
- ORCID:
- 0000-0002-1937-4091
+ Greiff, V
- Institution:
- University of Oslo
- Role:
- Examiner
- ORCID:
- 0000-0003-2622-5032
+ Engineering and Physical Sciences Research Council
More from this funder
- Funder identifier:
- http://dx.doi.org/10.13039/501100000265
- Grant:
- EP/L016044/1
- Programme:
- EPSRC and MRC Centre for Doctoral Training in Systems Approaches to Biomedical Science
+ Medical Research Council
More from this funder
- Grant:
- EP/L016044/1
- Programme:
- EPSRC and MRC Centre for Doctoral Training in Systems Approaches to Biomedical Science
- DOI:
- Type of award:
- DPhil
- Level of award:
- Doctoral
- Awarding institution:
- University of Oxford
- Language:
-
English
- Keywords:
- Subjects:
- Deposit date:
-
2021-03-05
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