Evidence map›Paper›PMID 31728204›Full record

ArticleNPJ systems biology and applications2019

From expression footprints to causal pathways: contextualizing large signaling networks with CARNIVAL.

Anika Liu, Panuwat Trairatphisan, Enio Gjerga, Athanasios Didangelos, Jonathan Barratt, Julio Saez-Rodriguez

Open access · goldAbstract read
In one paragraph

Article in NPJ systems biology and applications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 1 pooled it
7.9field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.

  1. Pooled it
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  15. Logic-based machine learning predicts how escitalopram attenuates cardiomyocyte hypertrophy.Proceedings of the National Academy of Sciences of the United States of America · 2025
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29 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 2 countries.

Anika Liu *Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute of Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.
Panuwat Trairatphisan *Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute of Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.ORCID 0000-0001-9015-5855
Enio Gjerga *Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute of Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.ORCID 0000-0001-8042-0395
Athanasios Didangelos3Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Jonathan Barratt3Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
Julio Saez-RodriguezHeidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute of Computational Biomedicine, Bioquant, 69120 Heidelberg, Germany.ORCID 0000-0002-8552-8976
Heidelberg University · DEUniversity of Leicester · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While gene expression profiling is commonly used to gain an overview of cellular processes, the identification of upstream processes that drive expression changes remains a challenge. To address this issue, we introduce CARNIVAL, a causal network contextualization tool which derives network architectures from gene expression footprints. CARNIVAL (CAusal Reasoning pipeline for Network identification using Integer VALue programming) integrates different sources of prior knowledge including signed and directed protein-protein interactions, transcription factor targets, and pathway signatures. The use of prior knowledge in CARNIVAL enables capturing a broad set of upstream cellular processes and regulators, leading to a higher accuracy when benchmarked against related tools. Implementation as an integer linear programming (ILP) problem guarantees efficient computation. As a case study, we applied CARNIVAL to contextualize signaling networks from gene expression data in IgA nephropathy (IgAN), a condition that can lead to chronic kidney disease. CARNIVAL identified specific signaling pathways and associated mediators dysregulated in IgAN including Wnt and TGF-β, which we subsequently validated experimentally. These results demonstrated how CARNIVAL generates hypotheses on potential upstream alterations that propagate through signaling networks, providing insights into diseases.

Indexed as

AlgorithmsComputational BiologyGene Expression ProfilingGene Expression RegulationGene Regulatory NetworksHumansMicroarray AnalysisProgramming, LinearSignal TransductionSoftwareTranscription FactorsTranscription FactorsRegulatory networksSoftware

Identifiers

PMID31728204
PMCPMC6848167
OpenAlexW2986455832

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.