Skipper analysis of eCLIP datasets enables sensitive detection of constrained translation factor binding sites.
Cell genomics
· 2023
· Vol. 3
(6)
· pp. 100317
Abstract
Technology for crosslinking and immunoprecipitation (CLIP) followed by sequencing (CLIP-seq) has identified the transcriptomic targets of hundreds of RNA-binding proteins in cells. To increase the power of existing and future CLIP-seq datasets, we introduce Skipper, an end-to-end workflow that converts unprocessed reads into annotated binding sites using an improved statistical framework. Compared with existing methods, Skipper on average calls 210%-320% more transcriptomic binding sites and sometimes >1,000% more sites, providing deeper insight into post-transcriptional gene regulation. Skipper also calls binding to annotated repetitive elements and identifies bound elements for 99% of enhanced CLIP experiments. We perform nine translation factor enhanced CLIPs and apply Skipper to learn determinants of translation factor occupancy, including transcript region, sequence, and subcellular localization. Furthermore, we observe depletion of genetic variation in occupied sites and nominate transcripts subject to selective constraint because of translation factor occupancy. Skipper offers fast, easy, customizable, and state-of-the-art analysis of CLIP-seq data.
Publication Types
["Journal Article"]
Keywords
MeSH Terms
[]
Funding
U24 HG009889
NHGRI NIH HHS
(United States)
S10 OD026929
NIH HHS
(United States)
R01 HG004659
NHGRI NIH HHS
(United States)
RF1 MH126719
NIMH NIH HHS
(United States)
R01 HG011864
NHGRI NIH HHS
(United States)
U41 HG009889
NHGRI NIH HHS
(United States)
S10 OD025052
NIH HHS
(United States)
Linked Datasets (2)
RPS19 binding with and without Diamond-Blackfan anemia variants
Homo sapiens44 data files
| File | Type | Size |
|---|---|---|
| RPS19-101m-2_S11_L001_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-101m-2_S11_L001_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-101m-2_S11_L002_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-101m-2_S11_L002_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-101m-3_S12_L001_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-101m-3_S12_L001_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-101m-3_S12_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-101m-3_S12_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-62m-1_S7_L001_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-62m-1_S7_L001_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-62m-1_S7_L002_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-62m-1_S7_L002_R1_001.fastq.gz | RIP-Seq | 1.1 GB |
| RPS19-62m-2_S8_L001_R1_001.fastq.gz | RIP-Seq | 1.0 GB |
| RPS19-62m-2_S8_L001_R1_001.fastq.gz | RIP-Seq | 1.0 GB |
| RPS19-62m-2_S8_L002_R1_001.fastq.gz | RIP-Seq | 1.0 GB |
| RPS19-62m-2_S8_L002_R1_001.fastq.gz | RIP-Seq | 1.0 GB |
| RPS19-62m-3_S9_L001_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-62m-3_S9_L001_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-62m-3_S9_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-62m-3_S9_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-IN-1_S1_L001_R1_001.fastq.gz | RIP-Seq | 1.3 GB |
| RPS19-IN-1_S1_L001_R1_001.fastq.gz | RIP-Seq | 1.3 GB |
| RPS19-IN-1_S1_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-IN-1_S1_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-IN-2_S2_L001_R1_001.fastq.gz | RIP-Seq | 1.4 GB |
| RPS19-IN-2_S2_L001_R1_001.fastq.gz | RIP-Seq | 1.4 GB |
| RPS19-IN-2_S2_L002_R1_001.fastq.gz | RIP-Seq | 1.4 GB |
| RPS19-IN-2_S2_L002_R1_001.fastq.gz | RIP-Seq | 1.4 GB |
| RPS19-IN-3_S3_L001_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-IN-3_S3_L001_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-IN-3_S3_L002_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-IN-3_S3_L002_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-WT-1_S4_L001_R1_001.fastq.gz | RIP-Seq | 1.3 GB |
| RPS19-WT-1_S4_L001_R1_001.fastq.gz | RIP-Seq | 1.3 GB |
| RPS19-WT-1_S4_L002_R1_001.fastq.gz | RIP-Seq | 1.3 GB |
| RPS19-WT-1_S4_L002_R1_001.fastq.gz | RIP-Seq | 1.3 GB |
| RPS19-WT-2_S5_L001_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-WT-2_S5_L001_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-WT-2_S5_L002_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-WT-2_S5_L002_R1_001.fastq.gz | RIP-Seq | 1.5 GB |
| RPS19-WT-3_S6_L001_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-WT-3_S6_L001_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-WT-3_S6_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
| RPS19-WT-3_S6_L002_R1_001.fastq.gz | RIP-Seq | 1.2 GB |
Skipper analysis of RNA-protein interactions highlights depletion of genetic variation in translation factor binding sites
Homo sapiens96 data files
| File | Type | Size |
|---|---|---|
| EIF2B5-IN1_S1_L001_R1_001.fastq.gz | RNA-Seq | 121.2 MB |
| EIF2B5-IN1_S1_L001_R1_001.fastq.gz | RNA-Seq | 121.2 MB |
| EIF2B5-IN1_S1_L002_R1_001.fastq.gz | RNA-Seq | 121.4 MB |
| EIF2B5-IN1_S1_L002_R1_001.fastq.gz | RNA-Seq | 121.4 MB |
| EIF2B5-IN2_S2_L001_R1_001.fastq.gz | RNA-Seq | 69.7 MB |
| EIF2B5-IN2_S2_L001_R1_001.fastq.gz | RNA-Seq | 69.7 MB |
| EIF2B5-IN2_S2_L002_R1_001.fastq.gz | RNA-Seq | 70.4 MB |
| EIF2B5-IN2_S2_L002_R1_001.fastq.gz | RNA-Seq | 70.4 MB |
| EIF2B5-IP1-_S3_L001_R1_001.fastq.gz | RNA-Seq | 136.7 MB |
| EIF2B5-IP1-_S3_L001_R1_001.fastq.gz | RNA-Seq | 136.7 MB |
| EIF2B5-IP1-_S3_L002_R1_001.fastq.gz | RNA-Seq | 135.2 MB |
| EIF2B5-IP1-_S3_L002_R1_001.fastq.gz | RNA-Seq | 135.2 MB |
| EIF2B5-IP2-_S4_L001_R1_001.fastq.gz | RNA-Seq | 122.7 MB |
| EIF2B5-IP2-_S4_L001_R1_001.fastq.gz | RNA-Seq | 122.7 MB |
| EIF2B5-IP2-_S4_L002_R1_001.fastq.gz | RNA-Seq | 121.5 MB |
| EIF2B5-IP2-_S4_L002_R1_001.fastq.gz | RNA-Seq | 121.5 MB |
| EIF2D--IN1-_S9_L001_R1_001.fastq.gz | RNA-Seq | 189.9 MB |
| EIF2D--IN1-_S9_L001_R1_001.fastq.gz | RNA-Seq | 189.9 MB |
| EIF2D--IN1-_S9_L002_R1_001.fastq.gz | RNA-Seq | 190.0 MB |
| EIF2D--IN1-_S9_L002_R1_001.fastq.gz | RNA-Seq | 190.0 MB |
| EIF2D--IN2_S10_L001_R1_001.fastq.gz | RNA-Seq | 145.3 MB |
| EIF2D--IN2_S10_L001_R1_001.fastq.gz | RNA-Seq | 145.3 MB |
| EIF2D--IN2_S10_L002_R1_001.fastq.gz | RNA-Seq | 146.6 MB |
| EIF2D--IN2_S10_L002_R1_001.fastq.gz | RNA-Seq | 146.6 MB |
| EIF2D--IP1-_S11_L001_R1_001.fastq.gz | RNA-Seq | 234.5 MB |
| EIF2D--IP1-_S11_L001_R1_001.fastq.gz | RNA-Seq | 234.5 MB |
| EIF2D--IP1-_S11_L002_R1_001.fastq.gz | RNA-Seq | 233.6 MB |
| EIF2D--IP1-_S11_L002_R1_001.fastq.gz | RNA-Seq | 233.6 MB |
| EIF2D--IP2-_S12_L001_R1_001.fastq.gz | RNA-Seq | 196.6 MB |
| EIF2D--IP2-_S12_L001_R1_001.fastq.gz | RNA-Seq | 196.6 MB |
| EIF2D--IP2-_S12_L002_R1_001.fastq.gz | RNA-Seq | 195.6 MB |
| EIF2D--IP2-_S12_L002_R1_001.fastq.gz | RNA-Seq | 195.6 MB |
| EIF2S2--IN1-_S13_L001_R1_001.fastq.gz | RNA-Seq | 129.8 MB |
| EIF2S2--IN1-_S13_L001_R1_001.fastq.gz | RNA-Seq | 129.8 MB |
| EIF2S2--IN1-_S13_L002_R1_001.fastq.gz | RNA-Seq | 129.4 MB |
| EIF2S2--IN1-_S13_L002_R1_001.fastq.gz | RNA-Seq | 129.4 MB |
| EIF2S3-IN2-_S14_L001_R1_001.fastq.gz | RNA-Seq | 117.0 MB |
| EIF2S3-IN2-_S14_L001_R1_001.fastq.gz | RNA-Seq | 117.0 MB |
| EIF2S3-IN2-_S14_L002_R1_001.fastq.gz | RNA-Seq | 117.1 MB |
| EIF2S3-IN2-_S14_L002_R1_001.fastq.gz | RNA-Seq | 117.1 MB |
| EIF2S4-IP1-_S15_L001_R1_001.fastq.gz | RNA-Seq | 134.6 MB |
| EIF2S4-IP1-_S15_L001_R1_001.fastq.gz | RNA-Seq | 134.6 MB |
| EIF2S4-IP1-_S15_L002_R1_001.fastq.gz | RNA-Seq | 133.3 MB |
| EIF2S4-IP1-_S15_L002_R1_001.fastq.gz | RNA-Seq | 133.3 MB |
| EIF2S5-IP2-_S16_L001_R1_001.fastq.gz | RNA-Seq | 208.3 MB |
| EIF2S5-IP2-_S16_L001_R1_001.fastq.gz | RNA-Seq | 208.3 MB |
| EIF2S5-IP2-_S16_L002_R1_001.fastq.gz | RNA-Seq | 206.2 MB |
| EIF2S5-IP2-_S16_L002_R1_001.fastq.gz | RNA-Seq | 206.2 MB |
| EIF3J-In1_S43_L002_R1_001.fastq.gz | RNA-Seq | 360.4 MB |
| EIF3J-In1_S43_L002_R1_001.fastq.gz | RNA-Seq | 360.4 MB |
| EIF3J-In2_S44_L002_R1_001.fastq.gz | RNA-Seq | 658.4 MB |
| EIF3J-In2_S44_L002_R1_001.fastq.gz | RNA-Seq | 658.4 MB |
| EIF3J-IP1_S45_L002_R1_001.fastq.gz | RNA-Seq | 654.1 MB |
| EIF3J-IP1_S45_L002_R1_001.fastq.gz | RNA-Seq | 654.1 MB |
| EIF3J-IP2_S46_L002_R1_001.fastq.gz | RNA-Seq | 808.5 MB |
| EIF3J-IP2_S46_L002_R1_001.fastq.gz | RNA-Seq | 808.5 MB |
| IN1_RPS14_S22_L001_R1_001.fastq.gz | RNA-Seq | 513.9 MB |
| IN1_RPS14_S22_L001_R1_001.fastq.gz | RNA-Seq | 513.9 MB |
| IN2_RPS14_S23_L001_R1_001.fastq.gz | RNA-Seq | 617.8 MB |
| IN2_RPS14_S23_L001_R1_001.fastq.gz | RNA-Seq | 617.8 MB |
| IP1_RPS14_S24_L001_R1_001.fastq.gz | RNA-Seq | 958.1 MB |
| IP1_RPS14_S24_L001_R1_001.fastq.gz | RNA-Seq | 958.1 MB |
| IP2_RPS14_S25_L001_R1_001.fastq.gz | RNA-Seq | 256.4 MB |
| IP2_RPS14_S25_L001_R1_001.fastq.gz | RNA-Seq | 256.4 MB |
| RPL29_IN1_S21_L001_R1_001.fastq.gz | RNA-Seq | 1.8 GB |
| RPL29_IN1_S21_L001_R1_001.fastq.gz | RNA-Seq | 1.8 GB |
| RPL29_IN2_S22_L001_R1_001.fastq.gz | RNA-Seq | 1.8 GB |
| RPL29_IN2_S22_L001_R1_001.fastq.gz | RNA-Seq | 1.8 GB |
| RPL29_IP1_S23_L001_R1_001.fastq.gz | RNA-Seq | 1.5 GB |
| RPL29_IP1_S23_L001_R1_001.fastq.gz | RNA-Seq | 1.5 GB |
| RPL29_IP2_S24_L001_R1_001.fastq.gz | RNA-Seq | 1.5 GB |
| RPL29_IP2_S24_L001_R1_001.fastq.gz | RNA-Seq | 1.5 GB |
| RPL35A_IN1_S29_L001_R1_001.fastq.gz | RNA-Seq | 1.3 GB |
| RPL35A_IN1_S29_L001_R1_001.fastq.gz | RNA-Seq | 1.3 GB |
| RPL35A_IN2_S30_L001_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| RPL35A_IN2_S30_L001_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| RPL35A_IP1_S31_L001_R1_001.fastq.gz | RNA-Seq | 2.6 GB |
| RPL35A_IP1_S31_L001_R1_001.fastq.gz | RNA-Seq | 2.6 GB |
| RPL35A_IP2_S32_L001_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| RPL35A_IP2_S32_L001_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| RPS19_IN1_S5_L001_R1_001.fastq.gz | RNA-Seq | 511.1 MB |
| RPS19_IN1_S5_L001_R1_001.fastq.gz | RNA-Seq | 511.1 MB |
| RPS19_IN2_S6_L001_R1_001.fastq.gz | RNA-Seq | 592.9 MB |
| RPS19_IN2_S6_L001_R1_001.fastq.gz | RNA-Seq | 592.9 MB |
| RPS19_IP1_S13_L001_R1_001.fastq.gz | RNA-Seq | 634.1 MB |
| RPS19_IP1_S13_L001_R1_001.fastq.gz | RNA-Seq | 634.1 MB |
| RPS19_IP2_S14_L001_R1_001.fastq.gz | RNA-Seq | 505.0 MB |
| RPS19_IP2_S14_L001_R1_001.fastq.gz | RNA-Seq | 505.0 MB |
| RPS3A_IN1_S25_L001_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| RPS3A_IN1_S25_L001_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| RPS3A_IN2_S26_L001_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| RPS3A_IN2_S26_L001_R1_001.fastq.gz | RNA-Seq | 1.2 GB |
| RPS3A_IP1_S27_L001_R1_001.fastq.gz | RNA-Seq | 941.6 MB |
| RPS3A_IP1_S27_L001_R1_001.fastq.gz | RNA-Seq | 941.6 MB |
| RPS3A_IP2_S28_L001_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
| RPS3A_IP2_S28_L001_R1_001.fastq.gz | RNA-Seq | 1.4 GB |
Potentially Related Datasets (3)
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
Skipper analysis of RNA-protein interactions highlights depletion of genetic variation in translation factor binding sites
Analysis Pipelines (3)
GSE138197 Data Processing
6 steps
geo_data_processing
GSE138197
GSE213867 eCLIP Data Processing
5 steps
GSE224998 eCLIP Data Processing
6 steps