publications

2024

1. Nat Commun

   An Integrated Technology for Quantitative Wide Mutational Scanning of Human Antibody Fab Libraries

   Brian M. Petersen, Monica B. Kirby, Karson M. Chrispens, and 11 more authors

   Nature Communications, May 2024

   Abs Bib HTML

   Antibodies are engineerable quantities in medicine. Learning antibody molecular recognition would enable the in silico design of high affinity binders against nearly any proteinaceous surface. Yet, publicly available experiment antibody sequence-binding datasets may not contain the mutagenic, antigenic, or antibody sequence diversity necessary for deep learning approaches to capture molecular recognition. In part, this is because limited experimental platforms exist for assessing quantitative and simultaneous sequence-function relationships for multiple antibodies. Here we present MAGMA-seq, an integrated technology that combines multiple antigens and multiple antibodies and determines quantitative biophysical parameters using deep sequencing. We demonstrate MAGMA-seq on two pooled libraries comprising mutants of nine different human antibodies spanning light chain gene usage, CDR H3 length, and antigenic targets. We demonstrate the comprehensive mapping of potential antibody development pathways, sequence-binding relationships for multiple antibodies simultaneously, and identification of paratope sequence determinants for binding recognition for broadly neutralizing antibodies (bnAbs). MAGMA-seq enables rapid and scalable antibody engineering of multiple lead candidates because it can measure binding for mutants of many given parental antibodies in a single experiment.

   @article{petersenIntegratedTechnologyQuantitative2024,
     title = {An Integrated Technology for Quantitative Wide Mutational Scanning of Human Antibody {{Fab}} Libraries},
     author = {Petersen, Brian M. and Kirby, Monica B. and Chrispens, Karson M. and Irvin, Olivia M. and Strawn, Isabell K. and Haas, Cyrus M. and Walker, Alexis M. and Baumer, Zachary T. and Ulmer, Sophia A. and Ayala, Edgardo and Rhodes, Emily R. and Guthmiller, Jenna J. and Steiner, Paul J. and Whitehead, Timothy A.},
     year = {2024},
     month = may,
     journal = {Nature Communications},
     volume = {15},
     number = {1},
     pages = {3974},
     publisher = {Nature Publishing Group},
     issn = {2041-1723},
     doi = {10.1038/s41467-024-48072-z},
     urldate = {2024-05-16},
     copyright = {2024 The Author(s)},
     langid = {english},
     keywords = {Antibodies,Applied immunology,Assay systems,Molecular engineering},
   }