PMID- 27684477 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231111 IS - 1553-7358 (Electronic) IS - 1553-734X (Print) IS - 1553-734X (Linking) VI - 12 IP - 9 DP - 2016 Sep TI - Exome Sequencing and Prediction of Long-Term Kidney Allograft Function. PG - e1005088 LID - 10.1371/journal.pcbi.1005088 [doi] LID - e1005088 AB - Current strategies to improve graft outcome following kidney transplantation consider information at the human leukocyte antigen (HLA) loci. Cell surface antigens, in addition to HLA, may serve as the stimuli as well as the targets for the anti-allograft immune response and influence long-term graft outcomes. We therefore performed exome sequencing of DNA from kidney graft recipients and their living donors and estimated all possible cell surface antigens mismatches for a given donor/recipient pair by computing the number of amino acid mismatches in trans-membrane proteins. We designated this tally as the allogenomics mismatch score (AMS). We examined the association between the AMS and post-transplant estimated glomerular filtration rate (eGFR) using mixed models, considering transplants from three independent cohorts (a total of 53 donor-recipient pairs, 106 exomes, and 239 eGFR measurements). We found that the AMS has a significant effect on eGFR (mixed model, effect size across the entire range of the score: -19.4 [-37.7, -1.1], P = 0.0042, chi2 = 8.1919, d.f. = 1) that is independent of the HLA-A, B, DR matching, donor age, and time post-transplantation. The AMS effect is consistent across the three independent cohorts studied and similar to the strong effect size of donor age. Taken together, these results show that the AMS, a novel tool to quantify amino acid mismatches in trans-membrane proteins in individual donor/recipient pair, is a strong, robust predictor of long-term graft function in kidney transplant recipients. FAU - Mesnard, Laurent AU - Mesnard L AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, United States of America; Department of Physiology and Biophysics, The Weill Cornell Medical College, New York, New York, United States of America. AD - INSERM UMR1155 et Service des Urgences Nephrologiques et Transplantation Renale, APHP, Hopital Tenon, Paris, France. AD - Sorbonne Universites, UPMC Universite Paris 06, Paris, France. FAU - Muthukumar, Thangamani AU - Muthukumar T AD - Division of Nephrology and Hypertension, Weill Cornell Medical College, New York, New York, United States of America. AD - Department of Transplantation Medicine, New York Presbyterian Hospital, New York, New York, United States of America. FAU - Burbach, Maren AU - Burbach M AD - Division of Nephrology and Hypertension, Weill Cornell Medical College, New York, New York, United States of America. FAU - Li, Carol AU - Li C AD - Division of Nephrology and Hypertension, Weill Cornell Medical College, New York, New York, United States of America. FAU - Shang, Huimin AU - Shang H AD - Genomics Core Facility, Weill Cornell Medical College, New York, New York, United States of America. FAU - Dadhania, Darshana AU - Dadhania D AD - Division of Nephrology and Hypertension, Weill Cornell Medical College, New York, New York, United States of America. AD - Department of Transplantation Medicine, New York Presbyterian Hospital, New York, New York, United States of America. FAU - Lee, John R AU - Lee JR AD - Division of Nephrology and Hypertension, Weill Cornell Medical College, New York, New York, United States of America. AD - Department of Transplantation Medicine, New York Presbyterian Hospital, New York, New York, United States of America. FAU - Sharma, Vijay K AU - Sharma VK AUID- ORCID: 0000-0003-4016-9911 AD - Division of Nephrology and Hypertension, Weill Cornell Medical College, New York, New York, United States of America. FAU - Xiang, Jenny AU - Xiang J AD - Genomics Core Facility, Weill Cornell Medical College, New York, New York, United States of America. FAU - Suberbielle, Caroline AU - Suberbielle C AD - Laboratoire d'histocompatibilite Hopital Saint Louis APHP, Paris, France. FAU - Carmagnat, Maryvonnick AU - Carmagnat M AD - Laboratoire d'histocompatibilite Hopital Saint Louis APHP, Paris, France. FAU - Ouali, Nacera AU - Ouali N AD - INSERM UMR1155 et Service des Urgences Nephrologiques et Transplantation Renale, APHP, Hopital Tenon, Paris, France. FAU - Rondeau, Eric AU - Rondeau E AD - INSERM UMR1155 et Service des Urgences Nephrologiques et Transplantation Renale, APHP, Hopital Tenon, Paris, France. AD - Sorbonne Universites, UPMC Universite Paris 06, Paris, France. FAU - Friedewald, John J AU - Friedewald JJ AUID- ORCID: 0000-0002-9344-9928 AD - Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. FAU - Abecassis, Michael M AU - Abecassis MM AD - Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. FAU - Suthanthiran, Manikkam AU - Suthanthiran M AD - Division of Nephrology and Hypertension, Weill Cornell Medical College, New York, New York, United States of America. AD - Department of Transplantation Medicine, New York Presbyterian Hospital, New York, New York, United States of America. FAU - Campagne, Fabien AU - Campagne F AUID- ORCID: 0000-0001-6237-3564 AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York, United States of America; Department of Physiology and Biophysics, The Weill Cornell Medical College, New York, New York, United States of America. LA - eng PT - Journal Article DEP - 20160929 PL - United States TA - PLoS Comput Biol JT - PLoS computational biology JID - 101238922 PMC - PMC5042552 COIS- LM, TM, MS and FC disclose that they are named inventors in a filed international patent application entitled "A METHOD TO MATCH ORGAN DONORS TO RECIPIENTS FOR TRANSPLANTATION". EDAT- 2016/09/30 06:00 MHDA- 2016/09/30 06:01 PMCR- 2016/09/29 CRDT- 2016/09/30 06:00 PHST- 2016/03/21 00:00 [received] PHST- 2016/07/26 00:00 [accepted] PHST- 2016/09/30 06:00 [entrez] PHST- 2016/09/30 06:00 [pubmed] PHST- 2016/09/30 06:01 [medline] PHST- 2016/09/29 00:00 [pmc-release] AID - PCOMPBIOL-D-16-00472 [pii] AID - 10.1371/journal.pcbi.1005088 [doi] PST - epublish SO - PLoS Comput Biol. 2016 Sep 29;12(9):e1005088. doi: 10.1371/journal.pcbi.1005088. eCollection 2016 Sep.