NDLI: Mining the antibodyome for HIV-1–neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains

Content Provider	PubMed Central
Author	Zhu, Jiang Ofek, Gilad Yang, Yongping Zhang, Baoshan Louder, Mark K. Gabriel, Lu Mckee, Krisha Pancera, Marie Skinner, Jeff Zhang, Zhenhai Parks, Robert Joshua, Eudailey Lloyd, Krissey E. Blinn, Julie Alam, S. Munir Haynes, Barton F. Simek, Melissa Burton, Dennis R. Koff, Wayne C. Mullikin, James C. Mascola, John R. Shapiro, Lawrence Kwong, Peter D. Becker, Jesse Benjamin, Betty Blakesley, Robert Bouffard, Gerry Brooks, Shelise Coleman, Holly Mila, Dekhtyar Gregory, Michael Guan, Xiaobin Gupta, Jyoti Han, Joel Hargrove, April Ho, Shi-ling Johnson, Taccara Legaspi, Richelle Lovett, Sean Maduro, Quino Masiello, Cathy Maskeri, Baishali Mcdowell, Jenny Montemayor, Casandra Mullikin, James Park, Morgan Riebow, Nancy Schandler, Karen Schmidt, Brian Sison, Christina Mal, Stantripop Thomas, James Thomas, Pam Vemulapalli, Meg Young, Alice
Abstract	Next-generation sequencing of antibody transcripts from HIV-1–infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and light-chain sequences from donor N152, the source of the broadly neutralizing antibody 10E8. We identified variants with up to 28% difference in amino acid sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants displayed similar architectures, and 10E8 variants reconstituted from matched and unmatched phylogenetic branches displayed significantly lower autoreactivity when matched. To test the generality of phylogenetic pairing, we analyzed donor International AIDS Vaccine Initiative 84, the source of antibodies PGT141–145. Heavy- and light-chain phylogenetic trees of PGT141–145 somatic variants also displayed remarkably similar architectures; in this case, branch pairings could be anchored by known PGT141–145 antibodies. Altogether, our findings suggest that phylogenetic matching of heavy and light chains can provide a means to approximate natural pairings.
Related Links	http://dx.doi.org/10.1073/pnas.1219320110
Ending Page	6475
Page Count	6
Starting Page	6470
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	16
Volume Number	110
Language	English
Publisher	National Academy of Sciences
Publisher Date	2013-04-16
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
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9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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