Evidence map›Paper›PMID 38378821›Full record

ArticleNature biomedical engineering2024

Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.

Yunhua Shi, Daniel Reker, James D Byrne, Ameya R Kirtane, Kaitlyn Hess, Zhuyi Wang, Natsuda Navamajiti, Cameron C Young, Zachary Fralish, Zilu Zhang and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.0field-weighted citation impact, top 12% 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

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. 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

17 authors at 5 institutions in 2 countries.

Yunhua Shi *Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Daniel Reker *Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4789-7380
James D ByrneKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ameya R KirtaneKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3779-0363
Kaitlyn HessKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Zhuyi WangKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Natsuda NavamajitiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0346-1756
Cameron C YoungDivision of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7323-4834
Zachary FralishDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Zilu ZhangDepartment of Biomedical Engineering, Duke University, Durham, NC, USA.
Aaron LopesKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Vance SoaresKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jacob WainerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4845-228X
Thomas von ErlachKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Lei MiaoKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Robert LangerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4255-0492
Giovanni TraversoKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. cgt20@mit.edu.ORCID http://orcid.org/0000-0001-7851-4077
Massachusetts Institute of Technology · USBrigham and Women's Hospital · USDuke University · USChulalongkorn University · THUniversity of Iowa · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
U.S. Department of Health & Human Services | National Institutes of Health (NIH) EB000244
6 · The paper itself

Abstract

In vitro systems that accurately model in vivo conditions in the gastrointestinal tract may aid the development of oral drugs with greater bioavailability. Here we show that the interaction profiles between drugs and intestinal drug transporters can be obtained by modulating transporter expression in intact porcine tissue explants via the ultrasound-mediated delivery of small interfering RNAs and that the interaction profiles can be classified via a random forest model trained on the drug-transporter relationships. For 24 drugs with well-characterized drug-transporter interactions, the model achieved 100% concordance. For 28 clinical drugs and 22 investigational drugs, the model identified 58 unknown drug-transporter interactions, 7 of which (out of 8 tested) corresponded to drug-pharmacokinetic measurements in mice. We also validated the model's predictions for interactions between doxycycline and four drugs (warfarin, tacrolimus, digoxin and levetiracetam) through an ex vivo perfusion assay and the analysis of pharmacologic data from patients. Screening drugs for their interactions with the intestinal transportome via tissue explants and machine learning may help to expedite drug development and the evaluation of drug safety.

Indexed as

IntestinesMachine LearningAnimalsBiological AvailabilityDrug InteractionsHumansMicePharmaceutical PreparationsSwinePharmaceutical Preparations

Identifiers

PMID38378821
OpenAlexW4391960362

What OpenQuestion holds

Textmetadata
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.