Felix Wong

Tao Shen, Zhihang Hu, Siqi Sun et al.

Accurate prediction of RNA three-dimensional (3D) structure remains an unsolved challenge. Determining RNA 3D structures is crucial for understanding their functions and informing RNA-targeting drug development and synthetic biology design. The structural flexibility of RNA, which leads to scarcity of experimentally determined data, complicates computational prediction efforts. Here, we present RhoFold+, an RNA language model-based deep learning method that accurately predicts 3D structures of single-chain RNAs from sequences. By integrating an RNA language model pre-trained on ~23.7 million RNA sequences and leveraging techniques to address data scarcity, RhoFold+ offers a fully automated end-to-end pipeline for RNA 3D structure prediction. Retrospective evaluations on RNA-Puzzles and CASP15 natural RNA targets demonstrate RhoFold+'s superiority over existing methods, including human expert groups. Its efficacy and generalizability are further validated through cross-family and cross-type assessments, as well as time-censored benchmarks. Additionally, RhoFold+ predicts RNA secondary structures and inter-helical angles, providing empirically verifiable features that broaden its applicability to RNA structure and function studies.

Alexander Peysakhovich, William Berman, Joseph Rufo et al.

Cell painting is a popular technique for creating human-interpretable, high-contrast images of cell morphology. There are two major issues with cell paint: (1) it is labor-intensive and (2) it requires chemical fixation, making the study of cell dynamics impossible. We train a diffusion model (Morphological Observation Neural Enhancement Tool, or MONET) on a large dataset to predict cell paint channels from brightfield images. We show that model quality improves with scale. The model uses a consistency architecture to generate time-lapse videos, despite the impossibility of obtaining cell paint video training data. In addition, we show that this architecture enables a form of in-context learning, allowing the model to partially transfer to out-of-distribution cell lines and imaging protocols. Virtual cell painting is not intended to replace physical cell painting completely, but to act as a complementary tool enabling novel workflows in biological research.

Cheng Li, Felix Wong, Zhenming Liu et al.

Discovering statistical structure from links is a fundamental problem in the analysis of social networks. Choosing a misspecified model, or equivalently, an incorrect inference algorithm will result in an invalid analysis or even falsely uncover patterns that are in fact artifacts of the model. This work focuses on unifying two of the most widely used link-formation models: the stochastic blockmodel (SBM) and the small world (or latent space) model (SWM). Integrating techniques from kernel learning, spectral graph theory, and nonlinear dimensionality reduction, we develop the first statistically sound polynomial-time algorithm to discover latent patterns in sparse graphs for both models. When the network comes from an SBM, the algorithm outputs a block structure. When it is from an SWM, the algorithm outputs estimates of each node's latent position.