Novel context-specific genome-scale modelling explores the potential of triacylglycerol production by Chlamydomonas reinhardtii
Bibliographic record
Abstract
Gene expression data of cell cultures is commonly measured in biological and medical studies to understand cellular decision-making in various conditions. Metabolism, affected but not solely determined by the expression, is much more difficult to measure experimentally. Finding a reliable method to predict cell metabolism for expression data will greatly benefit metabolic engineering. We have developed a novel pipeline, OVERLAY, that can explore cellular fluxomics from expression data using only a high-quality genome-scale metabolic model. This is done through two main steps: first, construct a protein-constrained metabolic model (PC-model) by integrating protein and enzyme information into the metabolic model (M-model). Secondly, overlay the expression data onto the PC-model using a novel two-step nonconvex and convex optimization formulation, resulting in a context-specific PC-model with optionally calibrated rate constants. The resulting model computes proteomes and intracellular flux states that are consistent with the measured transcriptomes. Therefore, it provides detailed cellular insights that are difficult to glean individually from the omic data or M-model alone. We apply the OVERLAY to interpret triacylglycerol (TAG) overproduction by Chlamydomonas reinhardtii, using time-course RNA-Seq data. We show that OVERLAY can compute C. reinhardtii metabolism under nitrogen deprivation and metabolic shifts after an acetate boost. OVERLAY can also suggest possible 'bottleneck' proteins that need to be overexpressed to increase the TAG accumulation rate, as well as discuss other TAG-overproduction strategies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".