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The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented…
A common problem in bioinformatics is related to identifying gene regulatory regions marked by relatively high frequencies of motifs, or deoxyribonucleic acid sequences that often code for transcription and enhancer proteins. Predicting…
Gene expression in cells is stochastic, yet differentiation is robust. We propose a mechanism in which frustrated genes with weakly stable intermediate expression undergo noise-driven switching between basins of attraction, followed by…
Foundation models in genomics have shown mixed success compared to their counterparts in natural language processing. Yet, the reasons for their limited effectiveness remain poorly understood. In this work, we investigate the role of…
The remarkable success of foundation models has sparked growing interest in their application to single-cell biology. Models like Geneformer and scGPT promise to serve as versatile tools in this specialized field. However, representing a…
Selective rationalization has become a common mechanism to ensure that predictive models reveal how they use any available features. The selection may be soft or hard, and identifies a subset of input features relevant for prediction. The…
Expression of cellular genes is regulated by binding of transcription factors to their promoter, either activating or inhibiting transcription of a gene. Particularly interesting is the case when the expressed protein regulates its own…
In human conversation an input post is open to multiple potential responses, which is typically regarded as a one-to-many problem. Promising approaches mainly incorporate multiple latent mechanisms to build the one-to-many relationship.…
We consider here the morphogenesis (pattern formation) problem for some genetic network models. First, we show that any given spatio-temporal pattern can be generated by a genetic network involving a sufficiently large number of genes.…
A theory for qualitative models of gene regulatory networks has been developed over several decades, generally considering transcription factors to regulate directly the expression of other transcription factors, without any intermediate…
Single-cell RNA-seq data allow the quantification of cell type differences across a growing set of biological contexts. However, pinpointing a small subset of genomic features explaining this variability can be ill-defined and…
Using an analytically solvable stochastic model, we study the properties of a simple genetic circuit consisting of multiple copies of an self-regulating gene. We analyse how the variation in gene copy number and the mutations changing the…
The purpose of this Note is twofold: First, we introduce the general formalism of evolutionary genetics dynamics involving fitnesses, under both the deterministic and stochastic setups, and chiefly in discrete-time. In the process, we…
In order to survive, reproduce and (in multicellular organisms) differentiate, cells must control the concentrations of the myriad different proteins that are encoded in the genome. The precision of this control is limited by the inevitable…
Memorization in language models is typically treated as a homogenous phenomenon, neglecting the specifics of the memorized data. We instead model memorization as the effect of a set of complex factors that describe each sample and relate it…
Populations of heterogeneous cells play an important role in many biological systems. In this paper we consider systems where each cell can be modelled by an ordinary differential equation. To account for heterogeneity, parameter values are…
A toggle switch consists of two genes that mutually repress each other. This regulatory motif is active during cell differentiation and is thought to act as a memory device, being able to choose and maintain cell fate decisions. In this…
In an attempt to explain the uniqueness of the coding mechanism of living cells as contrasted with multi-species structure of ecosystems we examine two models of individuals with some replicative properties. In the first model the system…
Cancer cells evolve through random somatic mutations. "Beneficial" mutations which disrupt key pathways (e.g. cell cycle regulation) are subject to natural selection. Multiple mutations may lead to the same "beneficial" effect, in which…
The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measurements using a host of different techniques including…