Evidence map›Paper›PMID 36519529›Full record

ArticleeLife2022

Structure-guided isoform identification for the human transcriptome.

Markus J Sommer, Sooyoung Cha, Ales Varabyou, Natalia Rincon, Sukhwan Park, Ilia Minkin, Mihaela Pertea, Martin Steinegger, Steven L Salzberg

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 47 citations in OpenAlex.

  1. A structure-aware generative AI framework for revealing functional relationships in protein families.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Testing the reliability of AI-generated protein structures.bioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
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  11. Isoswitching drives the aging process in human brains.bioRxiv : the preprint server for biology · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. Protein language models learn evolutionary statistics of interacting sequence motifs.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  16. Review
  17. Article
  18. bioRxiv : the preprint server for biology · 2024
    Article
  19. Predicting the Structural Impact of Human Alternative Splicing.bioRxiv : the preprint server for biology · 2023
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 3 countries.

Markus J SommerDepartment of Biomedical Engineering, Johns Hopkins School of Medicine and Whiting School of Engineering, Baltimore, United States.ORCID https://orcid.org/0000-0003-3414-1875
Sooyoung ChaSchool of Biological Sciences, Seoul National University, Seoul, Republic of Korea.ORCID https://orcid.org/0000-0001-7211-4603
Ales VarabyouCenter for Computational Biology, Johns Hopkins University, Baltimore, United States.
Natalia RinconDepartment of Biomedical Engineering, Johns Hopkins School of Medicine and Whiting School of Engineering, Baltimore, United States.
Sukhwan ParkSchool of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
Ilia MinkinDepartment of Biomedical Engineering, Johns Hopkins School of Medicine and Whiting School of Engineering, Baltimore, United States.
Mihaela PerteaDepartment of Biomedical Engineering, Johns Hopkins School of Medicine and Whiting School of Engineering, Baltimore, United States.
Martin Steinegger *School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
Steven L Salzberg *Department of Biomedical Engineering, Johns Hopkins School of Medicine and Whiting School of Engineering, Baltimore, United States.ORCID https://orcid.org/0000-0002-8859-7432
Johns Hopkins University · USSeoul National University · KR

Funding

Computational Methods for Genome Assembly, Transcript Assembly, and Variant DiscoveryR01HG006677 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI SALZBERG, STEVEN L. · 2011 to 2025
$10.7M
Computational Methods for Microbial and Microbiome Sequence AnalysisR35GM130151 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Steven L. Salzberg · 2019 to 2026
$2.9M
Comprehensive Human Expressed Sequences in Brain (CHESS-BRAIN) and their roles in neuropsychiatric illnessR01MH123567 · NIMH · JOHNS HOPKINS UNIVERSITY · PI SALZBERG, STEVEN L. · 2021 to 2025
$2.8M
NHGRI NIH HHS R01 HG006677NIGMS NIH HHS R35 GM130151NIMH NIH HHS R01 MH123567
6 · The paper itself

Abstract

Recently developed methods to predict three-dimensional protein structure with high accuracy have opened new avenues for genome and proteome research. We explore a new hypothesis in genome annotation, namely whether computationally predicted structures can help to identify which of multiple possible gene isoforms represents a functional protein product. Guided by protein structure predictions, we evaluated over 230,000 isoforms of human protein-coding genes assembled from over 10,000 RNA sequencing experiments across many human tissues. From this set of assembled transcripts, we identified hundreds of isoforms with more confidently predicted structure and potentially superior function in comparison to canonical isoforms in the latest human gene database. We illustrate our new method with examples where structure provides a guide to function in combination with expression and evolutionary evidence. Additionally, we provide the complete set of structures as a resource to better understand the function of human genes and their isoforms. These results demonstrate the promise of protein structure prediction as a genome annotation tool, allowing us to refine even the most highly curated catalog of human proteins. More generally we demonstrate a practical, structure-guided approach that can be used to enhance the annotation of any genome.

Indexed as

GenomeTranscriptomeHumansMolecular Sequence AnnotationProtein IsoformsSequence Analysis, RNAProtein Isoformsgeneticsgenome annotationgenomicshumanmachine learningmolecular biophysicsmouseprotein structure predictionproteomicsstructural biologytranscriptomics

Identifiers

PMID36519529
PMCPMC9812405
OpenAlexW4311579410

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.