A multi-stage representation of cell proliferation as a Markov process

Christian A Yates; Matthew J Ford; Richard L Mort

Home/Archive/arXiv

arXiv · 1705.09718

A multi-stage representation of cell proliferation as a Markov process

Christian A Yates·Matthew J Ford·Richard L Mort

View original source ↗Read source document ↗Export metadata ↓

Abstract

The stochastic simulation algorithm commonly known as Gillespie's algorithm is now used ubiquitously in the modelling of biological processes in which stochastic effects play an important role. In well-mixed scenarios at the sub-cellular level it is often reasonable to assume that times between successive reaction/interaction events are exponentially distributed and can be appropriately modelled as a Markov process and hence simulated by the Gillespie algorithm. However, Gillespie's algorithm is routinely applied to model biological systems for which it was never intended. In particular, processes in which cell proliferation is important should not be simulated naively using the Gillespie algorithm since the history-dependent nature of the cell cycle breaks the Markov process. The variance in experimentally measured cell cycle times is far less than in an exponential cell cycle time distribution with the same mean. Here we suggest a method of modelling the cell cycle that restores the memoryless property to the system and is therefore consistent with simulation via the Gillespie algorithm. By breaking the cell cycle into a number of independent exponentially distributed stages we can restore the Markov property at the same time as more accurately approximating the appropriate cell cycle time distributions. The consequences of our revised mathematical model are explored analytically. We demonstrate the importance of employing the correct cell cycle time distribution by considering two models incorporating cellular proliferation (one spatial and one non-spatial) and demonstrating that changing the cell cycle time distribution makes quantitative and qualitative differences to their outcomes. Our adaptation will allow modellers and experimentalists alike to appropriately represent cellular proliferation, whilst still being able to take advantage of the Gillespie algorithm.

Explore related subjects

q-bio.QM

Keep this discovery

BibTeX RIS

Christian A Yates, Matthew J Ford, Richard L Mort. 2017-05-26. A multi-stage representation of cell proliferation as a Markov process. https://arxiv.org/abs/1705.09718

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Biology-in-the-loop: Amortized Adaptive Hit Discovery in CRISPR Screens

Many biological discovery problems require experiments to be selected sequentially under constrained budgets. CRISPR screening is a prominent example, as exhaustive perturbation testing is often infeasible and candidate perturbations must instead be prioritized over multiple experimental rounds. Despite the importance of this problem, existing benchmarks for adaptive hit discovery remain limited in scale and diversity. Here, we introduce AssayBench-Loop, a large-scale benchmark for adaptive hit discovery comprising 1,389 CRISPR screens across five phenotype categories. Beyond enabling systematic evaluation, its scale makes it possible to learn acquisition strategies across historical experiments. Building on this resource, we introduce AssayLoop, a sequential experimental design framework combining AssayFormer, a transformer-based amortized acquisition policy trained across historical screens to adapt from experimental feedback, with LLM-derived biological priors through an adaptive handoff. In this view, completed experiments become training data for learning how accumulated evidence should guide what to test next, while LLMs provide prior biological knowledge to seed the search. We further introduce AssayLLM, showing that the same principle can be extended directly to an LLM through task-specific post-training. On temporally held-out screens, AssayLoop achieves a 5.67-fold enrichment over random selection and recovers 27.7% of hits after assaying approximately 5% of the candidate library, outperforming existing adaptive-design methods and standalone LLMs, and AssayFormer alone. Performance improves with increasing historical training data and transfers to phenotype categories excluded from training. These results demonstrate the value of learning acquisition policies across historical experiments and combining them with broad biological priors for efficient adaptive hit discovery.

q-bio.QM↗

arXiv2026

Multi-Task Bacterial Colony Detection and Classification Using YOLOv8 with Edge Optimization for Resource-Constrained Deployment

Manual counting and classification of bacterial colonies are critical yet labor-intensive tasks in microbiology, prone to human error particularly on densely populated plates. This work proposes a multi-task deep learning framework trained on the Annotated Germs for Automated Recognition (AGAR) dataset (18,000 images; 9,202 training / 3,067 testing) to automate Colony Forming Unit (CFU) enumeration and species classification. A custom multi-task CNN employing global regression served as the baseline, but demonstrated limited performance in clustered colony environments due to the absence of spatial localization. To address this, a YOLOv8 object detection architecture was adopted with high-resolution 1024x1024 inputs, enabling instance-level colony detection and label assignment. The model achieved a classification accuracy of 98.13% and a counting accuracy of 98.27% (within a 10-colony margin), demonstrating strong predictive capability. To bridge the gap between model performance and practical deployability, the trained model was optimized through unstructured and structured pruning, ONNX conversion, and reduced-precision inference (FP32, FP16, INT8). On a Raspberry Pi 4B, ONNX FP32 and FP16 variants offered the best balance between inference speed (~6.4s) and accuracy (MAE ~2.20). Unstructured pruning preserved predictive accuracy (MAE ~2.01) without runtime gains, while structured pruning resulted in significant accuracy degradation (MAE ~6.3), revealing the sensitivity of instance-level colony detection to architectural compression. These findings provide practical guidance for selecting optimization strategies in resource-constrained laboratory deployments.

q-bio.QM↗

arXiv2026

ADMET-EvO: a self-evolving scientific agent for sustained research across heterogeneous tasks

Scientific agents can move beyond automated model building by using accumulated evidence to revise both their questions and experimental strategies. The challenge is sustaining this adaptation across heterogeneous tasks without overfitting decisions to internal validation. Absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction provides a demanding setting across diverse assays, datasets and chemical domains. We therefore developed ADMET-EvO, an evidence-gated agent that formalizes endpoints, generates falsifiable hypotheses and tests interventions across data, feature and model axes. It carries supported, rejected and inconclusive outcomes forward to guide each new cycle. Across the 22-task Therapeutics Data Commons (TDC) ADMET benchmark, ADMET-EvO achieved the highest task-normalized score of 96.77. Evidence-guided selection reduced cumulative fitting time by 72.2% within a predefined non-inferiority margin. It also formalized 43 toxicity-related tasks and constructed endpoint-specific predictors. Together, these results show how ADMET-EvO can accumulate evidence, revise its strategy and expand its research scope over time.

q-bio.QM↗