Profiling immunoglobulin repertoires across multiple human tissues by RNA Sequencing

Serghei Mangul, Igor Mandric, Harry Taegyun Yang, Nicolas Strauli, Dennis Montoya, Jeremy Rotman, Will Van Der Wey, Jiem R. Ronas, Benjamin Statz, Douglas Yao, Alex Zelikovsky, Roberto Spreafico, Sagiv Shifman, Noah Zaitlen, Maura Rossetti, K. Mark Ansel, Eleazar Eskin

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Nov 09, 2018
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Received Date: 27th October 18

Assay-based approaches provide a detailed view of the adaptive immune system by profiling immunoglobulin (Ig) 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 immunoglobulin repertoire from regular RNA-Seq data. ImReP can also accurately assemble the complementary determining regions 3 (CDR3s), the most variable regions of Ig receptors. We applied our novel method to 8,555 samples across 53 tissues from 544 individuals in the Genotype-Tissue Expression (GTEx v6) project. ImReP is able to efficiently extract Ig-derived reads from RNA-Seq data. Using ImReP, we have created a systematic atlas of 3.6 million Ig sequences across a broad range of tissue types, most of which have not been studied for Ig receptor repertoires. We also compared the GTEx tissues to track the flow of Ig 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 Immunoglobulin Repertoires (The AIR), is freely available at https://github.com/smangul1/TheAIR/wiki , is one of the largest collection of CDR3 sequences and tissue types. We anticipate this recourse will enhance future immunology studies and advance the development of therapies for human diseases. ImReP is freely available at https://github.com/mandricigor/imrep/wiki

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.


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