RT Journal Article
SR Electronic
T1 Learning the high-dimensional immunogenomic features that predict public and private antibody repertoires
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 127902
DO 10.1101/127902
A1 Victor Greiff
A1 Cédric R. Weber
A1 Johannes Palme
A1 Ulrich Bodenhofer
A1 Enkelejda Miho
A1 Ulrike Menzel
A1 Sai T. Reddy
YR 2017
UL http://biorxiv.org/content/early/2017/04/17/127902.abstract
AB Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which are defined as antibody or T-cell receptor (TCR) clonal sequences shared across individuals. As of yet, it has remained unclear whether public clones possess predictable sequence features that separate them from private clones, which are believed to be generated largely stochastically. This knowledge gap represents a lack of insight into the shaping of immune repertoire diversity. Leveraging a machine learning approach capable of capturing the high-dimensional compositional information of each clonal sequence (defined by the complementarity determining region 3, CDR3), we detected predictive public- and private-clone-specific immunogenomic differences concentrated in the CDR3’s N1-D-N2 region, which allowed the prediction of public and private status with 80% accuracy in both humans and mice. Our results unexpectedly demonstrate that not only public but also private clones possess predictable high-dimensional immunogenomic features. Our support vector machine model could be trained effectively on large published datasets (3 million clonal sequences) and was sufficiently robust for public clone prediction across studies prepared with different library preparation and high-throughput sequencing protocols. In summary, we have uncovered the existence of high-dimensional immunogenomic rules that shape immune repertoire diversity in a predictable fashion. Our approach may pave the way towards the construction of a comprehensive atlas of public clones in immune repertoires, which may have applications in rational vaccine design and immunotherapeutics.