Evidence map›Paper›PMID 19412532›Full record

ArticlePLoS computational biology2009

A differential wiring analysis of expression data correctly identifies the gene containing the causal mutation.

Nicholas J Hudson, Antonio Reverter, Brian P Dalrymple

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

115 citing papers in PubMed, 1 synthesis or guideline pooled it, 231 citations in OpenAlex.

  1. Pooled it
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  8. Dissecting the Immune System through Gene Regulation.Advances in experimental medicine and biology · 2024
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  13. Network Analysis of Microarray Data.Methods in molecular biology (Clifton, N.J.) · 2022
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  20. Review

55 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

3 authors at 1 institution in 1 country.

Nicholas J HudsonFood Futures Flagship and Livestock Industries, Commonwealth Scientific and Industrial Research Organisation, Queensland Bioscience Precinct, St Lucia Brisbane, Queensland, Australia.
Antonio Reverter
Brian P Dalrymple
Animal, Food and Health Sciences · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Transcription factor (TF) regulation is often post-translational. TF modifications such as reversible phosphorylation and missense mutations, which can act independent of TF expression level, are overlooked by differential expression analysis. Using bovine Piedmontese myostatin mutants as proof-of-concept, we propose a new algorithm that correctly identifies the gene containing the causal mutation from microarray data alone. The myostatin mutation releases the brakes on Piedmontese muscle growth by translating a dysfunctional protein. Compared to a less muscular non-mutant breed we find that myostatin is not differentially expressed at any of ten developmental time points. Despite this challenge, the algorithm identifies the myostatin 'smoking gun' through a coordinated, simultaneous, weighted integration of three sources of microarray information: transcript abundance, differential expression, and differential wiring. By asking the novel question "which regulator is cumulatively most differentially wired to the abundant most differentially expressed genes?" it yields the correct answer, "myostatin". Our new approach identifies causal regulatory changes by globally contrasting co-expression network dynamics. The entirely data-driven 'weighting' procedure emphasises regulatory movement relative to the phenotypically relevant part of the network. In contrast to other published methods that compare co-expression networks, significance testing is not used to eliminate connections.

Indexed as

AlgorithmsGene Expression ProfilingOligonucleotide Array Sequence AnalysisAnimalsCattleCluster AnalysisComputer SimulationGene Expression RegulationMaleModels, GeneticMutation, MissenseMyostatinPhosphorylationRNA Processing, Post-TranscriptionalTranscription FactorsTranscription, GeneticMyostatinTranscription Factors

Identifiers

PMID19412532
PMCPMC2671163
OpenAlexW2139329624

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.