Dynamic modeling and analysis of cancer cellular network motifs
Bibliographic record
Abstract
With the advent of high-throughput biology, we now routinely scan cells and organisms at practically all levels, from genome to protein, metabolism, signaling and other cellular functions. This methodology allowed biological studies to move from a reductionist approach, such as isolation of specific pathways and mechanisms, to a more integrative approach, where biological systems are seen as a network of interconnected components that provide specific outputs and functions in response to stimuli. Recent literature on biological networks demonstrates two important concepts that we will consider in this review: (i) cellular pathways are highly interconnected and should not be studied separately, but as a network; (ii) simple, recurrent feedback motifs within the network can produce very specific functions that favor their modular use. The first theme differs from the traditional approach in biology because it provides a framework (i.e., the network view) in which large datasets are analyzed with an unbiased view. The second theme (feedback motifs) shows the importance of locally analyzing the dynamic properties of biological networks in order to better understand their functionality. We will review these themes with examples from cell signaling networks, gene regulatory networks and metabolic pathways. The deregulation of cellular networks (metabolism, signaling etc.) is involved in cancer, but the size of the networks and resulting non-linear behavior do not allow for intuitive reasoning. In that context, we argue that the qualitative classification of the 'building blocs' of biological networks (i.e. the motifs) in terms of dynamics and functionality will be critical to improve our understanding of cancer biology and rationalize the wealth of information from high-throughput experiments. From the examples highlighted in this review, it is clear that dynamic feedback motifs can be used to provide a unified view of various cellular processes involved in cancer and this will be critical for future research on personalized and predictive cancer therapies.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".