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View article: Proteome-wide model for human disease genetics
Proteome-wide model for human disease genetics Open
Missense variants remain a challenge in genetic interpretation owing to their subtle and context-dependent effects. Although current prediction models perform well in known disease genes, their scores are not calibrated across the proteome…
View article: Results of the Protein Engineering Tournament: An Open Science Benchmark for Protein Modeling and Design
Results of the Protein Engineering Tournament: An Open Science Benchmark for Protein Modeling and Design Open
The grand challenge of protein engineering is the development of computational models to characterize and generate protein sequences for arbitrary functions. Progress is limited by lack of (1) benchmarking opportunities, (2) large protein …
View article: Can protein expression be ‘solved’?
Can protein expression be ‘solved’? Open
Recombinant protein expression is central to biotechnology's application. However, not all proteins can be expressed in all organisms, and, given the vast experimental space, it can be challenging to identify the conditions that will yield…
View article: A Genomic Language Model for Zero-Shot Prediction of Promoter Variant Effects
A Genomic Language Model for Zero-Shot Prediction of Promoter Variant Effects Open
Disease-associated genetic variants occur extensively in noncoding regions like promoters, but current methods focus primarily on single nucleotide variants (SNVs) that typically have small regulatory effect sizes. Expanding beyond single …
View article: Results of the Protein Engineering Tournament: An Open Science Benchmark for Protein Modeling and Design
Results of the Protein Engineering Tournament: An Open Science Benchmark for Protein Modeling and Design Open
The grand challenge of protein engineering is the development of computational models to characterize and generate protein sequences for arbitrary functions. Progress is limited by lack of 1) benchmarking opportunities, 2) large protein fu…
View article: Deep generative modeling of the human proteome reveals over a hundred novel genes involved in rare genetic disorders
Deep generative modeling of the human proteome reveals over a hundred novel genes involved in rare genetic disorders Open
Identifying causal mutations accelerates genetic disease diagnosis, and therapeutic development. Missense variants present a bottleneck in genetic diagnoses as their effects are less straightforward than truncations or nonsense mutations. …
View article: ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction
ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction Open
Predicting the effects of mutations in proteins is critical to many applications, from understanding genetic disease to designing novel proteins that can address our most pressing challenges in climate, agriculture and healthcare. Despite …
View article: Proteome-wide model for human disease genetics
Proteome-wide model for human disease genetics Open
Identifying variants driving disease accelerates both genetic diagnosis and therapeutic development, but missense variants still present a bottleneck as their effects are less straightforward than truncations or nonsense mutations. While c…
View article: Continuous evolution of user-defined genes at 1-million-times the genomic mutation rate
Continuous evolution of user-defined genes at 1-million-times the genomic mutation rate Open
When nature maintains or evolves a gene’s function over millions of years at scale, it produces a diversity of homologous sequences whose patterns of conservation and change contain rich structural, functional, and historical information a…
View article: Removing bias in sequence models of protein fitness
Removing bias in sequence models of protein fitness Open
Unsupervised sequence models for protein fitness have emerged as powerful tools for protein design in order to engineer therapeutics and industrial enzymes, yet they are strongly biased towards potential designs that are close to their tra…