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Biology subjects

Hayes, T.

Publications and source records attributed to Hayes, T..

6 recordsLinked to original sources

Language Modeling Materializes a World Model of Protein Biology

Proteins are fundamental to life. The full extent of their biology is beyond our ability to characterize with experimental approaches in the physical laboratory. Accurate digital representations could accelerate the discovery of protein biology through virtual experiments. We propose language modeling to learn unified and general representations that can be scaled to all of protein biology. Building on these representations, we develop a structure prediction model that exceeds the performance of established methods for biomolecular complex prediction across benchmarks, including for the interactions of antibodies with their targets. A simple search procedure yields high experimental success rates for the discovery of proteins with nanomolar binding affinities for both miniproteins and single-chain antibodies, a modality critical for therapeutic design. Study of the concepts in the language models representation space reveals a systematic organization aligned with the reductionist understanding of proteins developed through empirical science. Leveraging this organization, we generate a comprehensive map of protein biology encompassing over 6.8 billion sequences and 1.1 billion predicted structures, identifying connections across known and unknown biology. As a whole, this shows language modeling as a powerful substrate for representing the biology of proteins, operating across scales from the prediction and design of protein interactions at the atomic level, to identifying properties of proteins at different levels of granularity and abstraction, to the scale of mapping connections between proteins across billions of years of evolution.

bioinformatics↗

4D bioprinting shape-morphing tissues in granular support hydrogels: Sculpting structure and guiding maturation

During embryogenesis, organs undergo dynamic shape transformations that sculpt their final shape, composition, and function. Despite this, current organ bioprinting approaches typically employ bioinks that restrict cell-generated morphogenetic behaviours resulting in structurally static tissues. Here, we introduce a novel platform that enables the bioprinting of tissues that undergo programmable and predictable 4D shape-morphing driven by cell-generated forces. Our method utilises embedded bioprinting to deposit collagen-hyaluronic acid bioinks within yield-stress granular support hydrogels that can accommodate and regulate 4D shape-morphing through their viscoelastic properties. Importantly, we demonstrate precise control over 4D shape-morphing by modulating factors such as the initial print geometry, cell phenotype, bioink composition, and support hydrogel viscoelasticity. Further, we observed that shape-morphing actively sculpts cell and extracellular matrix alignment along the principal tissue axis through a stress-avoidance mechanism. To enable predictive design of 4D shape-morphing patterns, we developed a finite element model that accurately captures shape evolution at both the cellular and tissue levels. Finally, we show that programmed 4D shape-morphing enhances the structural and functional properties of iPSC-derived heart tissues. This ability to design, predict, and program 4D shape-morphing holds great potential for engineering organ rudiments that recapitulate morphogenetic processes to sculpt their final shape, composition, and function.

bioengineering↗

Simulating 500 million years of evolution with a language model

More than three billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here we show that language models trained on tokens generated by evolution can act as evolutionary simulators to generate functional proteins that are far away from known proteins. We present ESM3, a frontier multimodal generative language model that reasons over the sequence, structure, and function of proteins. ESM3 can follow complex prompts combining its modalities and is highly responsive to biological alignment. We have prompted ESM3 to generate fluorescent proteins with a chain of thought. Among the generations that we synthesized, we found a bright fluorescent protein at far distance (58% identity) from known fluorescent proteins. Similarly distant natural fluorescent proteins are separated by over five hundred million years of evolution.

synthetic biology↗

Missing data approaches for longitudinal neuroimaging research: Examples from the Adolescent Brain and Cognitive Development (ABCD) Study

This paper addresses the challenges of managing missing values within expansive longitudinal neu-roimaging datasets, using the specific example of data derived from the Adolescent Brain and Cog-nitive Development (ABCD(R)) study. The conventional listwise deletion method, while widely used, is not recommended due to the risk that substantial bias can potentially be introduced with this method. Unfortunately, recommended alternative practices can be challenging to implement with large data sets. In this paper, we advocate for the adoption of more sophisticated statistical method-ologies, including multiple imputation, propensity score weighting, and full information maximum likelihood (FIML). Through practical examples and code using (ABCD(R)) data, we illustrate some of the benefits and challenges of these methods, with a review of how these advanced methodolo-gies bolster the robustness of analyses and contribute to the integrity of research findings in the field of developmental cognitive neuroscience.

neuroscience↗

Thermal asymmetries influence effects of warming on stage and size-dependent predator-prey interactions

Climate warming directly influences the developmental and feeding rates of organisms. Changes in these rates are likely to have consequences for species interactions, particularly for organisms affected by stage- or size-dependent predation. However, because of differences in species-specific responses to warming, predicting the impact of warming on predator and prey densities can be difficult. We present a general model of stage-dependent predation with temperature-dependent vital rates to explore the effects of warming when predator and prey have different thermal optima. We found that warming generally favored the interactor with the higher thermal optimum. Part of this effect occurred due to the stage-dependent nature of the interaction, and part due to thermal asymmetries. Furthermore, large differences in thermal optima between predators and prey (i.e., a high degree of asymmetry) led to a weaker interaction. Interestingly, below the predator and prey thermal optima, warming caused prey densities to decline, even as increasing temperature improved prey performance. We also parameterize our model using values from a well-studied system, Arctia virginalis and Formica lasioides, in which the predator has a warmer optimum. Overall, our results provide a general framework for understanding stage- and temperature-dependent predator-prey interactions, and illustrate that the thermal niche of both predator and prey are important to consider when predicting the effects of climate warming.

ecology↗

Sex differences in brain correlates of STEM anxiety

Anxiety is known to dysregulate the salience, default mode, and central executive networks of the human brain, yet this phenomenon has not been fully explored across the STEM learning experience, where anxiety can impact negatively academic performance. Here, we evaluated anxiety and large-scale brain connectivity in 101 undergraduate physics students. We found sex differences in STEM-related but not clinical anxiety, with longitudinal increases in science anxiety observed for both female and male students. Sex-specific impacts of STEM anxiety on brain connectivity emerged, with male students exhibiting distinct inter-network connectivity for STEM and clinical anxiety and female students demonstrating no significant within-sex correlations. Anxiety was negatively correlated with academic performance in sex-specific ways at both pre-and post-instruction. Moreover, math anxiety in male students mediated the relation between default mode-salience connectivity and course grade. Together, these results reveal complex sex differences in the neural mechanisms driving how anxiety impacts STEM learning.

neuroscience↗