Recent evidence from proteomics and deep massively parallel sequencing studies have revealed that eukaryotic genomes contain substantial numbers of as-yet-uncharacterized open reading frames (ORFs). We define these uncharacterized ORFs as novel ORFs (nORFs). nORFs in humans are mostly under 100 codons and are found in diverse regions of the genome, including in long noncoding RNAs, pseudogenes, 3′ UTRs, 5′ UTRs, and alternative reading frames of canonical protein coding exons.
The nORFs data set contains 233,232 ORFs curated from OpenProt and sORFs.org. These nORFs were annotated with respect to canonical transcripts and CDS, and they are found in diverse locations in the genomes such as overlapping canonical CDSs in alternate frames (altCDSs), in UTRs, in noncoding RNAs (ncRNAs), and in intronic/intergenic regions.
We used OpenProt (Release 1.3) and sORFs.org as the main sources for the nORFs data set. These databases were chosen for their commitment to providing consistent, verifiable, and maintained data.
Our curation process ensured that the final data set (1) contains only nORFs with translation evidence from either MS or ribosome profiling, (2) contains no duplicate or highly similar entries, and (3) contains only ORFs clearly distinct from currently annotated canonical proteins.
We annotated each nORF with reference to human GENCODE (v30) gene annotations. The annotation categories included nORFs mapping to UTRs or CDS of protein coding transcripts, ncRNAs, or intergenic regions.
We built an online platform with REST API functionality to make the nORFs data set easily accessible. The curated and annotated GRCh38 raw data set is available in BED and GTF formats, as well as a downloadable nORFs.org UCSC track. All coordinates in our database are in GRCh38. For the fully reproducible code used to generate these files, please refer to our GitHub repository.
For a comprehensive understanding of our methods and findings, please refer to our original research paper:
Neville MDC, Kohze R, Erady C, Meena N, Hayden M, Cooper DN, Mort M, Prabakaran S. A platform for curated products from novel open reading frames prompts reinterpretation of disease variants. Genome Res. 2021 Feb;31(2):327-336. doi: 10.1101/gr.263202.120. Epub 2021 Jan 19. PMID: 33468550; PMCID: PMC7849405.
The full text of this paper is available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849405/
For more detailed information about our methods, please refer to our published paper or contact us directly.