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Genome Biol. 2018 Feb 15;19(1):36. doi: 10.1186/s13059-018-1403-7.

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

Author information

1
Department of Computer Science, University of California, Los Angeles, CA, USA. smangul@ucla.edu.
2
Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, CA, USA. smangul@ucla.edu.
3
Department of Computer Science, University of California, Los Angeles, CA, USA.
4
Biomedical Sciences Graduate Program, University of California, San Francisco, CA, USA.
5
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
6
SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
7
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
8
Department of Bioengineering, University of California, Los Angeles, CA, USA.
9
Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA.
10
Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
11
Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
12
Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, CA, USA.
13
Department of Medicine, University of California, San Francisco, CA, USA.
14
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
15
Institute for Quantitative Biosciences, University of California, San Francisco, CA, USA.
16
Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
17
Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California, Los Angeles, CA, USA.
18
Department of Human Genetics, University of California, Los Angeles, CA, USA.
19
Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
20
Centro de Neumología Pediátrica, San Juan, Puerto Rico.
21
Schools of Pharmacy and Medicine, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
22
Department of Pediatrics, National Jewish Health, Denver, CO, USA.
23
University of Colorado School of Medicine, Denver, CO, USA.
24
Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
25
Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, CA, USA. Noah.Zaitlen@ucsf.edu.

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 .

PMID:
29548336
PMCID:
PMC5857127
DOI:
10.1186/s13059-018-1403-7
[Indexed for MEDLINE]
Free PMC Article

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