Evidence map›Paper›PMID 35456433›Full record

ArticleGenes2022

Novel Protein-Protein Interactions Highlighting the Crosstalk between Hypoplastic Left Heart Syndrome, Ciliopathies and Neurodevelopmental Delays.

Kalyani B Karunakaran, George C Gabriel, Narayanaswamy Balakrishnan, Cecilia W Lo, Madhavi K Ganapathiraju

Open access · goldAbstract read
In one paragraph

Article in Genes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. 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

5 authors at 2 institutions in 2 countries.

Kalyani B KarunakaranSupercomputer Education and Research Centre, Indian Institute of Science, Bangalore 560012, India.ORCID 0000-0003-1279-7750
George C GabrielDepartment of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15201, USA.
Narayanaswamy BalakrishnanSupercomputer Education and Research Centre, Indian Institute of Science, Bangalore 560012, India.
Cecilia W LoDepartment of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15201, USA.
Madhavi K GanapathirajuDepartment of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15206, USA.ORCID 0000-0002-3825-0924
University of Pittsburgh · USIndian Institute of Science Bangalore · IN

Funding

Sustaining the Expansion of the National Mesothelioma Virtual Bank (NMVB)U24OH009077 · OH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECICH, MICHAEL JOHN, DACIC, SANJA · 2008 to 2025
$18.0M
Cellular Approaches to Tissue Engineering/RegenerationT32EB001026 · NIBIB · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUNCAN, ANDREW W, MONGA, SATDARSHAN SINGH · 2003 to 2024
$5.5M
Discovery of Mental Health and Inflammation (MHAIN) InteractomeR01MH094564 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GANAPATHIRAJU, MADHAVI K · 2011 to 2015
$1.9M
Brain Abnormalities and Neurobehavioral Deficits in Hypoplastic Left Heart SyndromeF30HD097967 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GABRIEL, GEORGE CHRISTOPHER · 2019 to 2023
$238k
National Heart Lung and Blood Institute R01HL142788NIBIB NIH HHS T32 EB001026NICHD NIH HHS F30 HD097967NIMH NIH HHS R01 MH094564NIOSH CDC HHS U24 OH009077
6 · The paper itself

Abstract

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-Precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities. A total of 364 genes including 73 novel interactors were differentially regulated in tissue/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. We found that 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer's disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy- and microcephaly-associated genes, with the shared genes enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways, respectively. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly, respectively.

Indexed as

CiliopathiesHypoplastic Left Heart SyndromeInduced Pluripotent Stem CellsMicrocephalyNervous System MalformationsAnimalsHumansInfant, NewbornMiceMyocytes, Cardiaccongenital heart diseasedevelopmental disorderhypoplastic left heart syndromeinteractomeprotein–protein interactionsweb application

Identifiers

PMID35456433
PMCPMC9032108
OpenAlexW4225356257

What OpenQuestion holds

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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.