Evidence map›Paper›PMID 27522000›Full record

ArticleJournal of biomedical informatics2016

A model-driven methodology for exploring complex disease comorbidities applied to autism spectrum disorder and inflammatory bowel disease.

Judith Somekh, Mor Peleg, Alal Eran, Itay Koren, Ariel Feiglin, Alik Demishtein, Ruth Shiloh, Monika Heiner, Sek Won Kong, Zvulun Elazar and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biomedical informatics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Association of Autism Spectrum Disorders and Inflammatory Bowel Disease.Journal of autism and developmental disorders · 2018
    Article
  7. 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

11 authors at 5 institutions in 3 countries.

Judith SomekhDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Department of Information Systems, University of Haifa, Haifa, Israel. Electronic address: judith_somekh@hms.harvard.edu.
Mor PelegDepartment of Information Systems, University of Haifa, Haifa, Israel.
Alal EranDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA; Department of Life Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel.
Itay KorenDepartment of Genetics, Harvard Medical School, Boston, MA, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA.
Ariel FeiglinDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Alik DemishteinDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Ruth ShilohDepartment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Monika HeinerComputer Science Institute, Brandenburg University of Technology, Cottbus, Germany.
Sek Won KongComputational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.
Zvulun ElazarDepartment of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Isaac KohaneDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Weizmann Institute of Science · ILHarvard University · USBoston Children's Hospital · USBrandenburg University of Technology Cottbus-Senftenberg · DEUniversity of Haifa · IL

Funding

Modeling the temporal succession of phenotypes & environnnental cuesP50MH094267 · NIMH · UNIVERSITY OF CHICAGO · PI RZHETSKY, ANDREY · 2011 to 2015
$10.2M
An environment-wide association study in autism spectrum disorders using novel bioinformatics methods and metabolomics via mass spectrometryR01MH107205 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI KONG, SEK WON · 2015 to 2019
$2.1M
NIMH NIH HHS P50 MH094267NIMH NIH HHS R01 MH107205
6 · The paper itself

Abstract

We propose a model-driven methodology aimed to shed light on complex disorders. Our approach enables exploring shared etiologies of comorbid diseases at the molecular pathway level. The method, Comparative Comorbidities Simulation (CCS), uses stochastic Petri net simulation for examining the phenotypic effects of perturbation of a network known to be involved in comorbidities to predict new roles for mutations in comorbid conditions. To demonstrate the utility of our novel methodology, we investigated the molecular convergence of autism spectrum disorder (ASD) and inflammatory bowel disease (IBD) on the autophagy pathway. In addition to validation by domain experts, we used formal analyses to demonstrate the model's self-consistency. We then used CCS to compare the effects of loss of function (LoF) mutations previously implicated in either ASD or IBD on the autophagy pathway. CCS identified similar dynamic consequences of these mutations in the autophagy pathway. Our method suggests that two LoF mutations previously implicated in IBD may contribute to ASD, and one ASD-implicated LoF mutation may play a role in IBD. Future targeted genomic or functional studies could be designed to directly test these predictions.

Indexed as

MutationAutism Spectrum DisorderAutophagyComorbidityHumansInflammatory Bowel DiseasesPhenotypeASDAutismAutophagyIBDModelingPetri nets

Identifiers

PMID27522000
PMCPMC5155638
OpenAlexW2508440638

What OpenQuestion holds

Textmetadata
LicenceTDM
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.