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Biology subjects

Barozet, A.

Publications and source records attributed to Barozet, A..

2 recordsLinked to original sources

BOTANIC-1: a series of long-context plant genomic foundation models in the agentic era

The development of climate-resilient crops would be greatly accelerated by models able to reason directly over plant genomic sequences and to pinpoint trait-associated regions or loci. Anticipating the impact of DNA base changes (variants) remains challenging, and understanding regulatory mechanisms is still an active area of research. Through self-supervised training on unannotated genomic data, genomic language models (gLMs) can learn DNA syntax and grammar that go beyond current annotations, thus complementing standard bioinformatics analyses that rely on rules established by decades of genomics research. Here we present our agent-powered Model Factory and its first outputs: the Botanic1 family of gLMs designed for plant research, which operates reliably on sequences from hundreds of base pairs up to 128 kbp. These models outperform all generalist and plant-specific gLMs (as well as specialised baselines) on one of the largest sets of plant genomics evaluation tasks reported to date, at a much smaller budget than concurrent models. Mechanistic interpretability analysis identifies features associated with biologically meaningful sequence properties including coding region boundaries and splice site motifs, demonstrating that these models are a source of biological insight beyond their benchmark performance. Finally, because a gLM only becomes practically useful when embedded in a broader workflow, we integrate Botanic1 as a specialised genomic layer callable by a generalist large language model (LLM) agent, illustrating how such hybrid systems could accelerate plant biology research. To support the plant genomics research community, we release the four Botanic1 models, their pre-training corpus and the trained sparse autoencoder for research use at https://huggingface.co/spaces/living-models/botanic1-report.

plant biology↗

Conformational buffering underlies functional selection in intrinsically disordered protein regions

Many disordered proteins conserve essential functions in the face of extensive sequence variation. This makes it challenging to identify the forces responsible for functional selection. Viruses are robust model systems to investigate functional selection and they take advantage of protein disorder to acquire novel traits. Here, we combine structural and computational biophysics with evolutionary analysis to determine the molecular basis for functional selection in the intrinsically disordered adenovirus early gene 1A (E1A) protein. E1A competes with host factors to bind the retinoblastoma (Rb) protein, triggering early S-phase entry and disrupting normal cellular proliferation. We show that the ability to outcompete host factors depends on the picomolar binding affinity of E1A for Rb, which is driven by two binding motifs tethered by a hypervariable disordered linker. Binding affinity is determined by the spatial dimensions of the linker, which constrain the relative position of the two binding motifs. Despite substantial sequence variation across evolution, the linker dimensions are finely optimized through compensatory changes in amino acid sequence and sequence length, leading to conserved linker dimensions and maximal affinity. We refer to the mechanism that conserves spatial dimensions despite large-scale variations in sequence as conformational buffering. Conformational buffering explains how variable disordered proteins encode functions and could be a general mechanism for functional selection within disordered protein regions.

biophysics↗