Blending physics-based and inverse folding models to disentangle variant effects on stability and function

Protein sequences are constrained not only by the need to fold into stable structures, but also by specific functional requirements imposed by natural selection. Yet predictions of how amino-acid chan...

biorxiv.org

Beyond coverage tracks: fine-tuning AlphaGenome's splicing heads from scratch

Summary DeepMind has released AlphaGenome’s code and model weights, and the community has since developed alphagenome_ft and alphagenome-pytorch to enable seamless fine-tuning in both JAX and PyTorch....

genomicsxai.github.io

Exon inclusion signatures enable accurate estimation of splicing factor activity - Nature Communications

Splicing factors shape how genes are stitched into RNA, but their activity is hard to measure. Here, the authors benchmark network methods and show exon-inclusion signatures infer splicing factor acti...

nature.com

An information-theoretic argument for the restriction of the current biological alphabets to 4 nucleotides and 20 amino acids - Scientific Reports

Life as we know it is based on foldable biopolymers encoded with just 4 nucleotides or 20 amino acids. Evolution of these biopolymers requires effective and fast search of both the conformational spac...

nature.com

"La llengua de signes s'hauria d'estudiar a totes les escoles"

"El 2010 la llengua de signes catalana es va reconèixer a través d'una llei però això és teòric, falta portar-ho a la pràctica" "És important veure la llengua de signes catalana des de la perspectiva...

elpuntavui.cat

Proteome-wide model for human disease genetics

Nature Genetics - popEVE is a proteome-wide deep generative model to identify and predict pathogenicity of missense mutations causing genetic disorders.

rdcu.be

openreview.net

Using single-cell perturbation screens to decode the regulatory architecture of splicing factor programs

Abstract. Splicing factors shape the isoform pool of most transcribed genes, playing a critical role in cellular physiology. Their dysregulation is a hallm

doi.org

Decoding cnidarian cell type gene regulation

Animal cell types are defined by differential access to genomic information, a process orchestrated by the combinatorial activity of transcription factors that bind to cis -regulatory elements (CREs) to control gene expression. However, the regulatory logic and specific gene networks that define cell identities remain poorly resolved across the animal tree of life. As early-branching metazoans, cnidarians can offer insights into the early evolution of cell type-specific genome regulation. Here, we profiled chromatin accessibility in 60,000 cells from whole adults and gastrula-stage embryos of the sea anemone Nematostella vectensis. We identified 112,728 CREs and quantified their activity across cell types, revealing pervasive combinatorial enhancer usage and distinct promoter architectures. To decode the underlying regulatory grammar, we trained sequence-based models predicting CRE accessibility and used these models to infer ontogenetic relationships among cell types. By integrating sequence motifs, transcription factor expression, and CRE accessibility, we systematically reconstructed the gene regulatory networks that define cnidarian cell types. Our results reveal the regulatory complexity underlying cell differentiation in a morphologically simple animal and highlight conserved principles in animal gene regulation. This work provides a foundation for comparative regulatory genomics to understand the evolutionary emergence of animal cell type diversity. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, ERC-StG 851647 Ministerio de Ciencia e Innovación, https://ror.org/05r0vyz12, PID2021-124757NB-I00, FPI Severo Ochoa PhD fellowship European Union, https://ror.org/019w4f821, Marie Skłodowska-Curie INTREPiD co-fund agreement 75442, Marie Skłodowska-Curie grant agreement 101031767

biorxiv.org

Tomtom-lite: Accelerating Tomtom enables large-scale and real-time motif similarity scoring

Summary Pairwise sequence similarity is a core operation in genomic analysis, yet most attention has been given to sequences made up of discrete characters. With the growing prevalence of machine lear...

biorxiv.org

GitHub - MiqG/ColabRNA: Making RNA-based models accessible to all.

Making RNA-based models accessible to all. Contribute to MiqG/ColabRNA development by creating an account on GitHub.

github.com

The Genomic Code: the genome instantiates a generative model of the organism

How does the genome encode the form of the organism? What is the nature of this genomic code? Inspired by recent work in machine learning and neuroscience, we propose that the genome encodes a generat...

cell.com

Kolmogorov-Arnold Networks: the latest advance in Neural Networks, simply explained

The new type of network that is making waves in the ML world.

towardsdatascience.com

Protein codes promote selective subcellular compartmentalization

Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must assemble. Here, we demonstrate that prote...

science.org