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The adoption of deep learning techniques in genomics has been hindered by the difficulty of mechanistically interpreting the models that these techniques produce. In recent years, a variety of post-hoc attribution methods have been proposed…
Biological organisms are simple at heart: cells, their basic units, perform a variety of behaviors by expressing proteins from DNA-encoded genes. Gene expression though depends on sets of often-convoluted regulatory interactions known as…
Proteins are polymers of amino acids. These macromolecules are synthesized by intracellular machines called ribosomes. Although the experimental investigation of protein synthesis has been a traditional area of research in molecular cell…
Background: Elucidating gene regulatory networks is crucial for understanding normal cell physiology and complex pathologic phenotypes. Existing computational methods for the genome-wide ``reverse engineering'' of such networks have been…
Principles of feedback control have been shown to naturally arise in biological systems and successfully applied to build synthetic circuits. In this work we consider Biochemical Reaction Networks (CRNs) as a paradigm for modelling…
We examine the dynamics of the translation stage of cellular protein production, in which ribosomes move uni-directionally along mRNA strands building an amino acid chain as they go. We describe the system using a timed event graph - a…
Genetic robustness, the preservation of an optimal phenotype in the face of mutations, is critical to the understanding of evolution as phenotypically expressed genetic variation is the fuel of natural selection. The origin of genetic…
A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these…
Biopharmaceutical manufacturing is a rapidly growing industry with impact in virtually all branches of medicines. Biomanufacturing processes require close monitoring and control, in the presence of complex bioprocess dynamics with many…
This paper presents a real-time simulation involving ''protozoan-like'' cells that evolve by natural selection in a physical 2D ecosystem. Selection pressure is exerted via the requirements to collect mass and energy from the surroundings…
BioDynaMo is a biological processes simulator developed by an international community of researchers and software engineers working closely with neuroscientists. The authors have been working on gene expression, i.e. the process by which…
Auto-regulation, a process wherein a protein negatively regulates its own production, is a common motif in gene expression networks. Negative feedback in gene expression plays a critical role in buffering intracellular fluctuations in…
A blood cell lineage consists of several consecutive developmental stages from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks…
Cells control the size and organization of biomolecular condensates formed by liquid-liquid phase separation (LLPS), but multiple mechanisms likely contribute to this control and remain to be fully elucidated. Here we propose a…
The intrinsic stochasticity of gene expression can lead to large variability of protein levels across a population of cells. Variability (or noise) in protein distributions can be modulated by cellular mechanisms of gene regulation; in…
For the vast majority of genes in sequenced genomes, there is limited understanding of how they are regulated. Without such knowledge, it is not possible to perform a quantitative theory-experiment dialogue on how such genes give rise to…
Deciphering the control principles of metabolism and its interaction with other cellular functions is central to biomedicine and biotechnology. Yet, understanding the efficient control of metabolic fluxes remains elusive for large-scale…
The hierarchical organisation of cell identity is a fundamental feature of animal development with rich and well-characterized experimental phenomenology, yet the mechanisms driving its emergence remain unknown. The regulation of cell…
Decisions in the cell that lead to its ultimate fate are important for cellular functions such as proliferation, growth, differentiation, development and death. Understanding this decision process is imperative for advancements in the…
Recent whole genome polymerase binding assays have shown that a large proportion of unexpressed genes have pre-assembled RNA pol II transcription initiation complex stably bound to their promoters. Some such promoter proximally paused genes…