Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity - Statistical Genomics and Biological Physics Accéder directement au contenu
Article Dans Une Revue PLoS Computational Biology Année : 2016

Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity

Résumé

The immune system has developed a number of distinct complex mechanisms to shape and control the antibody repertoire. One of these mechanisms, the affinity maturation process, works in an evolutionary-like fashion: after binding to a foreign molecule, the antibody-producing B-cells exhibit a high-frequency mutation rate in the genome region that codes for the antibody active site. Eventually, cells that produce antibodies with higher affinity for their cognate antigen are selected and clonally expanded. Here, we propose a new statistical approach based on maximum entropy modeling in which a scoring function related to the binding affinity of antibodies against a specific antigen is inferred from a sample of sequences of the immune repertoire of an individual. We use our inference strategy to infer a statistical model on a data set obtained by sequencing a fairly large portion of the immune repertoire of an HIV-1 infected patient. The Pearson correlation coefficient between our scoring function and the IC50 neutralization titer measured on 30 different antibodies of known sequence is as high as 0.77 (p-value 10−6), outperforming other sequence- and structure-based models.
Fichier principal
Vignette du fichier
journal.pcbi.1004870.PDF (2.95 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-01333986 , version 1 (20-06-2016)

Licence

Paternité

Identifiants

Citer

Lorenzo Asti, Guido Uguzzoni, Paolo Marcatili, Andrea Pagnani. Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity. PLoS Computational Biology, 2016, 12 (4), pp.e1004870. ⟨10.1371/journal.pcbi.1004870⟩. ⟨hal-01333986⟩
129 Consultations
108 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More