ROP: Dumpster diving in RNA-sequencing to find the source of 1 trillion reads across diverse adult human tissues

Serghei Mangul, Harry Taegyun Yang, Nicolas Strauli, Franziska Gruhl, Hagit T. Porath, Kevin Hsieh, Linus Chen, Timothy Daley, Stephanie Christenson, Agata Wesolowska-Andersen, Roberto Spreafico, Cydney Rios, Celeste Eng, Andrew D. Smith, Ryan D. Hernandez, Roel A. Ophoff, Jose Rodriguez Santana, Erez Y. Levanon, Prescott G. Woodruff, Esteban BurchardMax A. Seibold, Sagiv Shifman, Eleazar Eskin, Noah Zaitlen

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

High-throughput RNA-sequencing (RNA-seq) technologies provide an unprecedented opportunity to explore the individual transcriptome. Unmapped reads are a large and often overlooked output of standard RNA-seq analyses. Here, we present Read Origin Protocol (ROP), a tool for discovering the source of all reads originating from complex RNA molecules. We apply ROP to samples across 2630 individuals from 54 diverse human tissues. Our approach can account for 99.9% of 1 trillion reads of various read length. Additionally, we use ROP to investigate the functional mechanisms underlying connections between the immune system, microbiome, and disease. ROP is freely available at https://github.com/smangul1/rop/wiki.

Original languageEnglish
Article number36
JournalGenome Biology
Volume19
Issue number1
DOIs
StatePublished - 15 Feb 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

Funding

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. SM and RS acknowledge support from a QCB Collaboratory Postdoctoral Fellowship, and the QCB Collaboratory community directed by Matteo Pellegrini. S.M. and E.E. are supported by National Science Foundation grants 0513612, 0731455, 0729049, 0916676, 1065276, 1302448, 1320589 and 1331176, and National Institutes of Health grants K25-HL080079, U01-DA024417, P01-HL30568, P01-HL28481, R01-GM083198, R01-ES021801, R01-MH101782 and R01-ES022282. SS was supported by the Israel Science Foundation (grant no. 688/12, 575/ 17). RDH was supported by 5R01HG007644. RAO was supported by R01MH090553. EYL was supported by the Israel Science Foundation (1380/ 14). PGW was supported by the following NIH grants: K24 HL137013, R01 HL095372 and a grant from Genentech Inc. NZ was supported by NIH NHLBI K25HL121295 and NIH NIDCR R03DE025665. EB was supported by the Sandler Family Foundation, the American Asthma Foundation, the RWJF Amos Medical Faculty Development Program, Harry Wm. and Diana V. Hind Distinguished Professor in Pharmaceutical Sciences II, National Institutes of Health 1R01HL117004, HL128439, MD010443, R01Hl128439, R01HL135156, 1X01HL134589 National Institute of Health and Environmental Health SciencesR01ES015794, R21ES24844, the National Institute on Minority Health and Health Disparities 1P60MD006902, U54MD009523, 1R01MD010443 and the Tobacco-Related Disease Research Program under Award Number 24RT-0025. TD and ADS were supported by NIH grant R01 HG007650. We thank the anonymous reviewers for comments on an initial draft of thismanuscript, which resulted in an improved publication. We thank Dr. Lana Martin for discussions and helpful comments on the manuscript. We thank Srilaxmi Nerella for help with data management. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. SM and RS acknowledge support from a QCB Collaboratory Postdoctoral Fellowship, and the QCB Collaboratory community directed by MatteoPellegrini. S.M. and E.E. are supported by National Science Foundation grants 0513612, 0731455, 0729049, 0916676, 1065276, 1302448, 1320589 and 1331176, and National Institutes of Health grants K25-HL080079, U01-DA024417, P01-HL30568, P01-HL28481, R01-GM083198, R01-ES021801, R01-MH101782 and R01-ES022282. SS was supported by the Israel Science Foundation (grant no. 688/12, 575/ 17). RDH was supported by 5R01HG007644. RAO was supported by R01MH090553. EYL was supported by the Israel Science Foundation (1380/ 14). PGW was supported by the following NIH grants: K24 HL137013, R01 HL095372 and a grant from Genentech Inc. NZ was supported by NIH NHLBI K25HL121295 and NIH NIDCR R03DE025665. EB was supported by the Sandler Family Foundation, the American Asthma Foundation, the RWJF Amos Medical Faculty Development Program, Harry Wm. and Diana V. Hind Distinguished Professor in Pharmaceutical Sciences II, National Institutes of Health 1R01HL117004, HL128439, MD010443, R01Hl128439, R01HL135156, 1X01HL134589 National Institute of Health and Environmental Health Sciences R01ES015794, R21ES24844, the National Institute on Minority Health and Health Disparities 1P60MD006902, U54MD009523, 1R01MD010443 and the Tobacco-Related Disease Research Program under Award Number 24RT- 0025. TD and ADS were supported by NIH grant R01 HG007650.

FundersFunder number
National Institute of Health and Environmental Health SciencesR01ES015794
RWJF Amos Medical Faculty Development Program
National Science Foundation1302448, 0731455, 0513612, 0729049, 1065276, 1320589, 0916676, 1331176
National Institutes of HealthHL128439, R01-GM083198, R01 HL095372, R01-MH101782, U01-DA024417, R01-ES021801, P01-HL28481, R01-ES022282, R21ES24844, R01ES015794, K24 HL137013, R01Hl128439, K25-HL080079, 1R01HL117004, R01 HG007650, 1X01HL134589
National Heart, Lung, and Blood InstituteR01HL135156, K25HL121295, P01HL030568
National Institute of Dental and Craniofacial ResearchR03DE025665
Genentech
Tobacco-Related Disease Research Program24RT-0025
National Institute on Minority Health and Health Disparities1P60MD006902, MD010443, U54MD009523
Sandler Foundation
American Asthma Foundation
Israel Science Foundation5R01HG007644, R01MH090553, 1380/ 14, 575/ 17, 688/12
National Science Foundation

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