Daily Papers

Predicting transcriptional responses to specific perturbations is critical for understanding cellular regulatory mechanisms and accelerating drug discovery. Single-cell RNA sequencing destroys each measured cell, yielding only unpaired populations of control and perturbed cells. However, existing methods typically model perturbation prediction at the single-cell level and assume cell-to-cell correspondence, which conflicts with the unpaired nature of the observed data. To address this challenge, we propose PopPert, a framework that explicitly parameterizes population-level joint gene expression distributions for collective transcriptional state modeling. Given a control population distribution and a perturbation condition, PopPert predicts perturbation-induced changes in distribution parameters, eliminating the need for cell-level correspondence and reducing sensitivity to single-cell noise. To effectively capture gene co-expression patterns, PopPert leverages a low-rank Gaussian Copula to model cross-gene statistical dependencies and construct the joint gene expression distribution, additionally allowing sampling of synthetic perturbed single-cell profiles. Across multiple single-cell benchmarks spanning both genetic and chemical perturbations, PopPert achieves superior overall performance in differential expression recovery, perturbation effect estimation, and population-level distribution matching. These results establish population-level joint distribution learning as an effective paradigm for predicting transcriptional responses from unpaired single-cell populations. Code for PopPert is publicly available at https://github.com/whd1125/PopPert.

The increasing reliance on AI-driven solutions, particularly Large Language Models (LLMs) like the GPT series, for information retrieval highlights the critical need for their factuality and fairness, especially amidst the rampant spread of misinformation and disinformation online. Our study evaluates the factual accuracy, stability, and biases in widely adopted GPT models, including GPT-3.5 and GPT-4, contributing to reliability and integrity of AI-mediated information dissemination. We introduce 'Global-Liar,' a dataset uniquely balanced in terms of geographic and temporal representation, facilitating a more nuanced evaluation of LLM biases. Our analysis reveals that newer iterations of GPT models do not always equate to improved performance. Notably, the GPT-4 version from March demonstrates higher factual accuracy than its subsequent June release. Furthermore, a concerning bias is observed, privileging statements from the Global North over the Global South, thus potentially exacerbating existing informational inequities. Regions such as Africa and the Middle East are at a disadvantage, with much lower factual accuracy. The performance fluctuations over time suggest that model updates may not consistently benefit all regions equally. Our study also offers insights into the impact of various LLM configuration settings, such as binary decision forcing, model re-runs and temperature, on model's factuality. Models constrained to binary (true/false) choices exhibit reduced factuality compared to those allowing an 'unclear' option. Single inference at a low temperature setting matches the reliability of majority voting across various configurations. The insights gained highlight the need for culturally diverse and geographically inclusive model training and evaluation. This approach is key to achieving global equity in technology, distributing AI benefits fairly worldwide.