Step 4 · Discover

Knowledge gaps

Each gap is derived by comparing what your dataset shows against the curated evidence level of the surrounding mechanism. Nothing here is a claim — it is a question with a rationale.

Back to mechanism

Observed — Measured in the user's uploaded experiment.

Strong evidence — Supported by multiple relevant publications in a comparable context.

Limited evidence — Some evidence exists but it is sparse, indirect or context-dependent.

Conflicting evidence — Publications disagree about direction or existence of this relationship.

Predicted — Computational / AI inference. Not an experimental finding.

Unknown / knowledge gap — Insufficient evidence found in this biological context.

ERK1/2 → AS160

The curated relationship ERK1/2 → AS160 is classified as limited in cardiomyocytes.

Limited evidence

What is known

• ERK activity has been reported to contribute to AS160/TBC1D4 regulation, but the cardiomyocyte evidence is sparse.
• Other cell types: Better characterised in skeletal muscle and adipocytes.

What is not known

• Whether the relationship holds in erk1/2-perturbed cardiomyocytes at the timescale of your experiment.
• Whether the effect is direct or mediated by a parallel route.
• Which experimental conditions explain the contradictory reports.

Why this matters: Evidence exists but is sparse, indirect or from a different cell type, so extrapolation to cardiomyocytes is currently an assumption.

Adjacent literature

ERK-dependent regulation of GLUT4 trafficking in striated muscle

Demo placeholder record · Demo journal record · 2017 · Original research

rat · L6 myotubes

Placeholder for literature describing MAPK/ERK contribution to GLUT4 translocation, which is context-dependent and partly redundant with PI3K/AKT signalling.

Unverified demo record — no DOI/PMID, do not cite

PI3K/AKT, not MAPK, is required for insulin-stimulated GLUT4 translocation

Demo placeholder record · Demo journal record · 2014 · Original research

mouse · Isolated soleus muscle

Placeholder for the counter-position: MEK inhibition does not block insulin-stimulated GLUT4 translocation in several models, arguing ERK is modulatory rather than required.

Unverified demo record — no DOI/PMID, do not cite

Design experiment

ERK1/2 → GLUT4 translocation

The curated relationship ERK1/2 → GLUT4 translocation is classified as conflicting in cardiomyocytes.

Conflicting evidence

What is known

• Whether ERK signalling is required for GLUT4 translocation is disputed; several studies find MEK inhibition has no effect.
• Other cell types: Conflict is reported in skeletal muscle and adipocyte models as well.

What is not known

• Whether the relationship holds in erk1/2-perturbed cardiomyocytes at the timescale of your experiment.
• Whether the effect is direct or mediated by a parallel route.
• Which experimental conditions explain the contradictory reports.

Why this matters: Published results disagree. A well-powered experiment in a defined cardiomyocyte model could resolve the discrepancy rather than add to it.

Adjacent literature

ERK-dependent regulation of GLUT4 trafficking in striated muscle

Demo placeholder record · Demo journal record · 2017 · Original research

rat · L6 myotubes

Placeholder for literature describing MAPK/ERK contribution to GLUT4 translocation, which is context-dependent and partly redundant with PI3K/AKT signalling.

Unverified demo record — no DOI/PMID, do not cite

PI3K/AKT, not MAPK, is required for insulin-stimulated GLUT4 translocation

Demo placeholder record · Demo journal record · 2014 · Original research

mouse · Isolated soleus muscle

Placeholder for the counter-position: MEK inhibition does not block insulin-stimulated GLUT4 translocation in several models, arguing ERK is modulatory rather than required.

Unverified demo record — no DOI/PMID, do not cite

Design experiment

Transcription → PGC-1α

The curated relationship Transcription → PGC-1α is classified as limited in cardiomyocytes.

Limited evidence

What is known

• ERK-dependent transcriptional input to PGC-1α is reported, but direction is context-dependent.
• No cross-cell-type evidence indexed.

What is not known

• Whether the relationship holds in transcription-perturbed cardiomyocytes at the timescale of your experiment.
• Whether the effect is direct or mediated by a parallel route.
• Whether the effect size is large enough to be physiologically meaningful.

Why this matters: Evidence exists but is sparse, indirect or from a different cell type, so extrapolation to cardiomyocytes is currently an assumption.

Adjacent literature

Substrate shift toward fatty acid oxidation in the diabetic heart

Demo placeholder record · Demo journal record · 2013 · Review

human · Human heart / rodent models

Placeholder for the well-documented reduction in glucose utilisation and increased fatty acid oxidation in type 2 diabetic myocardium, with reduced cardiac efficiency.

Unverified demo record — no DOI/PMID, do not cite

Design experiment

S1PR1 → Mitochondrial respiration

The curated relationship S1PR1 → Mitochondrial respiration is classified as unknown in cardiomyocytes.

Unknown / knowledge gap

What is known

• A direct S1PR1 → mitochondrial respiration relationship in cardiomyocytes is hypothesised from adjacent evidence. No direct experimental demonstration was found in this context.
• Other cell types: Sparse, mostly non-cardiac reports link S1P receptor signalling to bioenergetics.

What is not known

• Whether the relationship holds in s1pr1-perturbed cardiomyocytes at the timescale of your experiment.
• Whether the effect is direct or mediated by a parallel route.
• Whether the effect size is large enough to be physiologically meaningful.

Why this matters: No direct experimental demonstration was found in this cell type. Adjacent steps are supported, so the missing link is testable with a focused loss-of-function design.

Design experiment