Learning the high-dimensional immunogenomic features that predict public and private antibody repertoires
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Autor:innen
Weber, Cédric R.
Palme, Johannes
Bodenhofer, Ulrich
Menzel, Ulrike
Reddy, Sai T.
Autor:in (Körperschaft)
Publikationsdatum
15.10.2017
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Journal of Immunology
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
199
Ausgabe / Nummer
8
Seiten / Dauer
2985-2997
Patentnummer
Verlag / Herausgebende Institution
American Association of Immunologists
Verlagsort / Veranstaltungsort
Rockville
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
Recent studies have revealed that immune repertoires contain a substantial fraction of public clones, which may be defined as Ab or TCR clonal sequences shared across individuals. It has remained unclear whether public clones possess predictable sequence features that differentiate 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 CDR3), we detected predictive public clone and private clone–specific immunogenomic differences concentrated in CDR3’s N1–D–N2 region, which allowed the prediction of public and private status with 80% accuracy in humans and mice. Our results unexpectedly demonstrate that public, as well as 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 individuals and 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 for the construction of a comprehensive atlas of public mouse and human immune repertoires with potential applications in rational vaccine design and immunotherapeutics.
Schlagwörter
Fachgebiet (DDC)
600 - Technik, Medizin, angewandte Wissenschaften
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
0022-1767
1550-6606
1550-6606
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Nein
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Closed
Lizenz
Zitation
GREIFF, Victor, Cédric R. WEBER, Johannes PALME, Ulrich BODENHOFER, Enkelejda MIHO, Ulrike MENZEL und Sai T. REDDY, 2017. Learning the high-dimensional immunogenomic features that predict public and private antibody repertoires. Journal of Immunology. 15 Oktober 2017. Bd. 199, Nr. 8, S. 2985–2997. DOI 10.4049/jimmunol.1700594. Verfügbar unter: https://irf.fhnw.ch/handle/11654/46932