Samuel King

All Publications

• Sequence modeling and design from molecular to genome scale with Evo. Science (New York, N.Y.) Nguyen, E., Poli, M., Durrant, M. G., Kang, B., Katrekar, D., Li, D. B., Bartie, L. J., Thomas, A. W., King, S. H., Brixi, G., Sullivan, J., Ng, M. Y., Lewis, A., Lou, A., Ermon, S., Baccus, S. A., Hernandez-Boussard, T., Re, C., Hsu, P. D., Hie, B. L. 2024; 386 (6723): eado9336

  Abstract

  The genome is a sequence that encodes the DNA, RNA, and proteins that orchestrate an organism's function. We present Evo, a long-context genomic foundation model with a frontier architecture trained on millions of prokaryotic and phage genomes, and report scaling laws on DNA to complement observations in language and vision. Evo generalizes across DNA, RNA, and proteins, enabling zero-shot function prediction competitive with domain-specific language models and the generation of functional CRISPR-Cas and transposon systems, representing the first examples of protein-RNA and protein-DNA codesign with a language model. Evo also learns how small mutations affect whole-organism fitness and generates megabase-scale sequences with plausible genomic architecture. These prediction and generation capabilities span molecular to genomic scales of complexity, advancing our understanding and control of biology.

  View details for DOI 10.1126/science.ado9336

  View details for PubMedID 39541441

• Spatiotemporal modeling of molecular holograms. Cell Qiu, X., Zhu, D. Y., Lu, Y., Yao, J., Jing, Z., Min, K. H., Cheng, M., Pan, H., Zuo, L., King, S., Fang, Q., Zheng, H., Wang, M., Wang, S., Zhang, Q., Yu, S., Liao, S., Liu, C., Wu, X., Lai, Y., Hao, S., Zhang, Z., Wu, L., Zhang, Y., Li, M., Tu, Z., Lin, J., Yang, Z., Li, Y., Gu, Y., Ellison, D., Chen, A., Liu, L., Weissman, J. S., Ma, J., Xu, X., Liu, S., Bai, Y. 2024

  Abstract

  Quantifying spatiotemporal dynamics during embryogenesis is crucial for understanding congenital diseases. We developed Spateo (https://github.com/aristoteo/spateo-release), a 3D spatiotemporal modeling framework, and applied it to a 3D mouse embryogenesis atlas at E9.5 and E11.5, capturing eight million cells. Spateo enables scalable, partial, non-rigid alignment, multi-slice refinement, and mesh correction to create molecular holograms of whole embryos. It introduces digitization methods to uncover multi-level biology from subcellular to whole organ, identifying expression gradients along orthogonal axes of emergent 3D structures, e.g., secondary organizers such as midbrain-hindbrain boundary (MHB). Spateo further jointly models intercellular and intracellular interaction to dissect signaling landscapes in 3D structures, including the zona limitans intrathalamica (ZLI). Lastly, Spateo introduces "morphometric vector fields" of cell migration and integrates spatial differential geometry to unveil molecular programs underlying asymmetrical murine heart organogenesis and others, bridging macroscopic changes with molecular dynamics. Thus, Spateo enables the study of organ ecology at a molecular level in 3D space over time.

  View details for DOI 10.1016/j.cell.2024.10.011

  View details for PubMedID 39532097

• Forecasting SARS-CoV-2 spike protein evolution from small data by deep learning and regression Frontiers in Systems Biology King, S., Chen, X. E., Ng, S. W., Rostin, K., Hahn, S. V., Roberts, T., Schwab, J. C., Sekhon, P., Kagieva, M., Reilly, T., Qi, R., Salman, P., Hong, R. J., Ma, E. J., Hallam, S. J. 2024; 4

  View details for DOI 10.3389/fsysb.2024.1284668

• DNA-GPS: A theoretical framework for optics-free spatial genomics and synthesis of current methods. Cell systems Greenstreet, L., Afanassiev, A., Kijima, Y., Heitz, M., Ishiguro, S., King, S., Yachie, N., Schiebinger, G. 2023

  Abstract

  While single-cell sequencing technologies provide unprecedented insights into genomic profiles at the cellular level, they lose the spatial context of cells. Over the past decade, diverse spatial transcriptomics and multi-omics technologies have been developed to analyze molecular profiles of tissues. In thisarticle, we categorize current spatial genomics technologies into three classes: optical imaging, positional indexing, and mathematical cartography. We discuss trade-offs in resolution and scale, identify limitations, and highlight synergies between existing single-cell and spatial genomics methods. Further, we propose DNA-GPS (global positioning system), a theoretical framework for large-scale optics-free spatial genomics that combines ideas from mathematical cartography and positional indexing. DNA-GPS has the potential to achieve scalable spatial genomics for multiple measurement modalities, andby eliminating the need for optical measurement, it has the potential to position cells in three-dimensions (3D).

  View details for DOI 10.1016/j.cels.2023.08.005

  View details for PubMedID 37751737

• Young innovators and the bioeconomy Genomics and the Global Bioeconomy Chen, X. E., King, S., Ng, S. W., Salman, P., Schwab, J. C., Sekhon, P. Academic Press. 2023; 1st: 83-100

  View details for DOI 10.1016/b978-0-323-91601-1.00005-5

• Subcellular coordination of plant cell wall synthesis DEVELOPMENTAL CELL Hoffmann, N., King, S., Samuels, A., McFarlane, H. E. 2021; 56 (7): 933-948

  Abstract

  Organelles of the plant cell cooperate to synthesize and secrete a strong yet flexible polysaccharide-based extracellular matrix: the cell wall. Cell wall composition varies among plant species, across cell types within a plant, within different regions of a single cell wall, and in response to intrinsic or extrinsic signals. This diversity in cell wall makeup is underpinned by common cellular mechanisms for cell wall production. Cellulose synthase complexes function at the plasma membrane and deposit their product into the cell wall. Matrix polysaccharides are synthesized by a multitude of glycosyltransferases in hundreds of mobile Golgi stacks, and an extensive set of vesicle trafficking proteins govern secretion to the cell wall. In this review, we discuss the different subcellular locations at which cell wall synthesis occurs, review the molecular mechanisms that control cell wall biosynthesis, and examine how these are regulated in response to different perturbations to maintain cell wall homeostasis.

  View details for DOI 10.1016/j.devcel.2021.03.004

  View details for Web of Science ID 000641581300008

  View details for PubMedID 33761322