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 Mandric Igor 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 Douglas Yao A1 Alex Zelikovsky A1 Roberto Spreafico A1 Sagiv Shifman A1 Noah Zaitlen A1 Maura Rossetti A1 K. Mark Ansel A1 Eleazar Eskin YR 2017 UL http://biorxiv.org/content/early/2017/03/25/089235.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 carry 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 our novel method 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 RNA-Seq data. ImReP can also accurately assemble the complementary determining regions 3 (CDR3s), the most variable regions of B and T cell receptors, and determine their antigen specificity. Using ImReP, we have created a 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 also compared 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, and we examined the compositional similarities of clonal populations between these tissues. The atlas of T and B cell 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 immunology studies and advance development of therapies for human diseases. ImReP is freely available at https://sergheimangul.wordpress.com/imrep/.