RT Journal Article
SR Electronic
T1 Profiling adaptive immune repertoires across multiple human tissues by RNA Sequencing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 089235
DO 10.1101/089235
A1 Serghei Mangul
A1 Igor Mandric
A1 Harry Taegyun Yang
A1 Nicolas Strauli
A1 Dennis Montoya
A1 Jeremy Rotman
A1 Will Van Der Wey
A1 Jiem R. Ronas
A1 Benjamin Statz
A1 Alex Zelikovsky
A1 Roberto Spreafico
A1 Sagiv Shifman
A1 Noah Zaitlen
A1 Maura Rossetti
A1 K. Mark Ansel
A1 Eleazar Eskin
YR 2016
UL http://biorxiv.org/content/early/2016/11/22/089235.abstract
AB Assay-based approaches provide a detailed view of the adaptive immune system by profiling T and B cell receptor repertoires. However, these methods come at a high cost and lack the scale of standard RNA sequencing (RNA-seq). Here we report the development of ImReP, a novel computational method for rapid and accurate profiling of the adaptive immune repertoire from regular RNA-Seq data. We applied it to 8,555 samples across 544 individuals from 53 tissues from the Genotype-Tissue Expression (GTEx v6) project. ImReP is able to efficiently extract TCR- and BCR- derived reads from the RNA-Seq data and accurately assemble the complementarity determining regions 3 (CDR3s), the most variable regions of B- and T-cell receptors determining their antigen specificity. Using ImReP, we have created the systematic atlas of immunological sequences for B- and T-cell repertoires across a broad range of tissue types, most of which have not been studied for B and T cell receptor repertoires. We have also examined the compositional similarities of clonal populations between the GTEx tissues to track the flow of T- and B- clonotypes across immune-related tissues, including secondary lymphoid organs and organs encompassing mucosal, exocrine, and endocrine sites. The atlas of T- and B-cell receptor receptors, freely available at https://sergheimangul.wordpress.com/atlas-immune-repertoires/, is the largest collection of CDR3 sequences and tissue types. We anticipate this recourse will enhance future studies in areas such as immunology and advance development of therapies for human diseases. ImReP is freely available at https://sergheimangul.wordpress.com/imrep/.