Evidence map›Paper›PMID 31924844›Full record

ArticleScientific reports2020

In silico analysis of alternative splicing on drug-target gene interactions.

Yanrong Ji, Rama K Mishra, Ramana V Davuluri

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

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  6. Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025
    Review
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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

3 authors at 1 institution in 1 country.

Yanrong JiDivision of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-0134-664X
Rama K MishraThe Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, IL, USA.
Ramana V DavuluriDivision of Health and Biomedical Informatics, Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. ramana.davuluri@northwestern.edu.ORCID http://orcid.org/0000-0002-7053-1064
Northwestern University · US

Funding

Informatics Platform for Mammalian Gene Regulation at Isoform-levelR01LM011297 · NLM · WISTAR INSTITUTE · PI DAVULURI, RAMANA V · 2013 to 2020
$2.4M
NLM NIH HHS R01 LM011297
6 · The paper itself

Abstract

Identifying and evaluating the right target are the most important factors in early drug discovery phase. Most studies focus on one protein ignoring the multiple splice-variant or protein-isoforms, which might contribute to unexpected therapeutic activity or adverse side effects. Here, we present computational analysis of cancer drug-target interactions affected by alternative splicing. By integrating information from publicly available databases, we curated 883 FDA approved or investigational stage small molecule cancer drugs that target 1,434 different genes, with an average of 5.22 protein isoforms per gene. Of these, 618 genes have ≥5 annotated protein-isoforms. By analyzing the interactions with binding pocket information, we found that 76% of drugs either miss a potential target isoform or target other isoforms with varied expression in multiple normal tissues. We present sequence and structure level alignments at isoform-level and make this information publicly available for all the curated drugs. Structure-level analysis showed ligand binding pocket architectures differences in size, shape and electrostatic parameters between isoforms. Our results emphasize how potentially important isoform-level interactions could be missed by solely focusing on the canonical isoform, and suggest that on- and off-target effects at isoform-level should be investigated to enhance the productivity of drug-discovery research.

Indexed as

Alternative SplicingComputational BiologyComputer SimulationMolecular Targeted TherapyAmino Acid SequenceAntineoplastic AgentsGene Expression ProfilingModels, MolecularProtein ConformationProtein IsoformsSequence AlignmentAntineoplastic AgentsProtein Isoforms

Identifiers

PMID31924844
PMCPMC6954184
OpenAlexW3000224897

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.