ABSTRACT
Our work seeks to transform how new and emergent variants of pandemic causing viruses, specially SARS-CoV-2, are identified and classified. By adapting large language models (LLMs) for genomic data, we build genome-scale language models (GenSLMs) which can learn the evolutionary landscape of SARS-CoV-2 genomes. By pre-training on over 110 million prokaryotic gene sequences, and then finetuning a SARS-CoV-2 specific model on 1.5 million genomes, we show that GenSLM can accurately and rapidly identify variants of concern. Thus, to our knowledge, GenSLM represents one of the first whole genome scale foundation models which can generalize to other prediction tasks. We demonstrate the scaling of GenSLMs on both GPU-based supercomputers and AI-hardware accelerators, achieving over 1.54 zettaflops in training runs. We present initial scientific insights gleaned from examining GenSLMs in tracking the evolutionary dynamics of SARS-CoV-2, noting that its full potential on large biological data is yet to be realized.
ABSTRACT
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g., cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale.