Whole-Genome Phenotype Prediction with Machine Learning: Open Problems in Bacterial Genomics

How can we identify causal genetic mechanisms that govern bacterial traits? Initial efforts entrusting machine learning models to handle the task of predicting phenotype from genotype return high accuracy scores. However, attempts to extract any meaning from the predictive models are found to be corrupted by falsely identified "causal" features. Relying solely on pattern recognition and correlations is unreliable, significantly so in bacterial genomics settings where high-dimensionality and spurious associations are the norm. Though it is not yet clear whether we can overcome this hurdle, significant efforts are being made towards discovering potential high-risk bacterial genetic variants. In view of this, we set up open problems surrounding phenotype prediction from bacterial whole-genome datasets and extending those to learning causal effects, and discuss challenges that impact the reliability of a machine's decision-making when faced with datasets of this nature.

Exploring the Limits of Fine-grained LLM-based Physics Inference via Premise Removal Interventions

Language models can hallucinate when performing complex and detailed mathematical reasoning. Physics provides a rich domain for assessing mathematical reasoning capabilities where physical context imbues the use of symbols which needs to satisfy complex semantics (\textit{e.g.,} units, tensorial order), leading to instances where inference may be algebraically coherent, yet unphysical. In this work, we assess the ability of Language Models (LMs) to perform fine-grained mathematical and physical reasoning using a curated dataset encompassing multiple notations and Physics subdomains. We improve zero-shot scores using synthetic in-context examples, and demonstrate non-linear degradation of derivation quality with perturbation strength via the progressive omission of supporting premises. We find that the models' mathematical reasoning is not physics-informed in this setting, where physical context is predominantly ignored in favour of reverse-engineering solutions.