Muhammad Arif Nadeem

Kirill Vishniakov, Boulbaba Ben Amor, Engin Tekin et al.

We introduce Gene42, a novel family of Genomic Foundation Models (GFMs) designed to manage context lengths of up to 192,000 base pairs (bp) at a single-nucleotide resolution. Gene42 models utilize a decoder-only (LLaMA-style) architecture with a dense self-attention mechanism. Initially trained on fixed-length sequences of 4,096 bp, our models underwent continuous pretraining to extend the context length to 192,000 bp. This iterative extension allowed for the comprehensive processing of large-scale genomic data and the capture of intricate patterns and dependencies within the human genome. Gene42 is the first dense attention model capable of handling such extensive long context lengths in genomics, challenging state-space models that often rely on convolutional operators among other mechanisms. Our pretrained models exhibit notably low perplexity values and high reconstruction accuracy, highlighting their strong ability to model genomic data. Extensive experiments on various genomic benchmarks have demonstrated state-of-the-art performance across multiple tasks, including biotype classification, regulatory region identification, chromatin profiling prediction, variant pathogenicity prediction, and species classification. The models are publicly available at huggingface.co/inceptionai.

Mohammad Amaan Sayeed, Engin Tekin, Maryam Nadeem et al.

Unlocking the next generation of biotechnology and therapeutic innovation demands overcoming the inherent complexity and resource-intensity of conventional protein engineering methods. Recent GenAI-powered computational techniques often rely on the availability of the target protein's 3D structures and specific binding sites to generate high-affinity binders, constraints exhibited by models such as AlphaProteo and RFdiffusion. In this work, we explore the use of Protein Language Models (pLMs) for high-affinity binder generation. We introduce Prot42, a novel family of Protein Language Models (pLMs) pretrained on vast amounts of unlabeled protein sequences. By capturing deep evolutionary, structural, and functional insights through an advanced auto-regressive, decoder-only architecture inspired by breakthroughs in natural language processing, Prot42 dramatically expands the capabilities of computational protein design based on language only. Remarkably, our models handle sequences up to 8,192 amino acids, significantly surpassing standard limitations and enabling precise modeling of large proteins and complex multi-domain sequences. Demonstrating powerful practical applications, Prot42 excels in generating high-affinity protein binders and sequence-specific DNA-binding proteins. Our innovative models are publicly available, offering the scientific community an efficient and precise computational toolkit for rapid protein engineering.