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Biology subjects

Nemeth, M.

Publications and source records attributed to Nemeth, M..

4 recordsLinked to original sources

Flexible belief updating drives the childhood advantage in statistical learning

Children often outperform adults in probabilistic statistical learning tasks, yet the mechanisms underlying this developmental advantage remain poorly understood. Here, we used eye-tracking measures of belief updating to examine how children and adults acquire and update predictions in a probabilistic sequence-learning task. Using the standard (oculomotor) reaction time measure, children showed stronger statistical learning than adults, replicating previous behavioral findings while revealing a more detailed profile of developmental differences in statistical learning. Critically, children updated their predictions more frequently: they were less likely to repeat previous predictions and more likely to shift their expectations in response to new input. Adults, in contrast, showed greater persistence, tending to maintain prior predictions even when those predictions were inconsistent with the underlying statistical structure. Despite these pronounced differences in updating behavior, the processing and use of prediction errors were remarkably similar across age groups. These findings indicate that developmental differences in statistical learning do not primarily arise from how prediction errors are computed, but rather from how prior beliefs and incoming information are weighted during belief updating. Childrens enhanced learning may therefore reflect reduced reliance on stable priors and greater sensitivity to current sensory evidence, supporting a more exploratory learning strategy. Adults, by contrast, appear to favor an exploitative strategy that stabilizes existing predictions but reduces flexibility in probabilistic environments. More broadly, the results suggest that developmental changes in statistical learning may reflect age-related differences in how readily learners revise their predictions in response to incoming evidence. By integrating sensitive oculomotor measures with analyses that probe the mechanisms underlying belief updating, the present study provides a more fine-grained account of how predictive learning changes across development and offers a framework for reconciling previously inconsistent developmental findings in statistical learning.

neuroscience↗

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↗

Rewriting endogenous human transcripts with trans-splicing

Splicing bridges the gap between static DNA sequence and the diverse and dynamic set of protein products that execute a genes biological functions. While exon skipping technologies enable influence over splice site selection, many desired perturbations to the transcriptome require replacement or addition of exogenous exons to target mRNAs: for example, to replace disease-causing exons, repair truncated proteins, or engineer protein fusions. Here, we report the development of RNA-guided trans-splicing with Cas editor (RESPLICE), inspired by the rare, natural process of trans-splicing that joins exons from two distinct primary transcripts. RESPLICE uses two orthogonal RNA-targeting CRISPR effectors to co-localize a trans-splicing pre-mRNA and to inhibit the cis-splicing reaction, respectively. We demonstrate efficient, specific, and programmable trans-splicing of multi-kilobase RNA cargo into nine endogenous transcripts across two human cell types, achieving up to 45% trans-splicing efficiency in bulk, or 90% when sorting for high effector expression. Our results present RESPLICE as a new mode of RNA editing for fine-tuned and transient control of cellular programs without permanent alterations to the genetic code.

molecular biology↗

Systematic characterization of gene function in a photosynthetic organism

Photosynthetic organisms are essential for human life, yet most of their genes remain functionally uncharacterized. Single-celled photosynthetic model systems have the potential to accelerate our ability to connect genes to functions. Here, using a barcoded mutant library of the model eukaryotic alga Chlamydomonas reinhardtii, we determined the phenotypes of more than 58,000 mutants under more than 121 different environmental growth conditions and chemical treatments. 78% of genes are represented by at least one mutant that showed a phenotype, providing clues to the functions of thousands of genes. Mutant phenotypic profiles allow us to place known and previously uncharacterized genes into functional pathways such as DNA repair, photosynthesis, the CO2-concentrating mechanism, and ciliogenesis. We illustrate the value of this resource by validating novel phenotypes and gene functions, including the discovery of three novel components of a defense pathway that counteracts actin cytoskeleton inhibitors released by other organisms. The data also inform phenotype discovery in land plants: mutants in Arabidopsis thaliana genes exhibit similar phenotypes to those we observed in their Chlamydomonas homologs. We anticipate that this resource will guide the functional characterization of genes across the tree of life.

systems biology↗