compatibility
Protein Thoughts: Interpretable Reasoning with Tree of Thoughts and Embedding-Space Flow Matching for Protein-Protein Interaction Discovery
Yeon, Kingsley, Liu, Xuefeng, Ghosal, Promit
Protein-protein interactions (PPIs) govern nearly all cellular processes, yet computational methods for identifying binding partners typically produce ranked predictions without mechanistic justification. This creates a fundamental barrier to adoption because biologists cannot assess whether predictions reflect genuine biochemical insight or spurious correlations. We present \textbf{Protein Thoughts}, a framework that reformulates PPI discovery as an interpretable search problem with explicit reasoning. The system decomposes binding evidence into four biologically meaningful signals: sequence similarity reflecting evolutionary relationships, structural complementarity capturing geometric fit, interface balance, and chemical compatibility encoding residue-level interactions. Rather than collapsing these signals into an opaque score, we preserve their individual contributions through a transparent value function that enables both ranking and auditing. To navigate large candidate spaces efficiently, we introduce hypothesis-guided entropy-regularized Tree-of-Thoughts search. A fine-tuned language model generates search directives from embedding-derived features, classifying candidates as high-priority, exploratory, or skippable. These directives condition a Boltzmann policy that balances exploitation with entropy-driven exploration, while hypothesis-aware pruning prevents premature abandonment of promising candidates. For candidates exhibiting score disagreement, hypothesis-conditioned embedding-space flow matching transports protein embeddings toward the binder manifold. On the SHS148k benchmark, Protein Thoughts achieves mean best-binder rank of 11.2 versus 47.7 for an entropic tree search baseline, a 76% improvement, and for binding prediction the trained value function achieves $91.08 \pm 0.19$ Micro-F1, outperforming existing PPI methods on the same dataset.
Qualitative Mechanism Independence
We define what it means for a joint probability distribution to be compatible with aset of independent causal mechanisms, at a qualitative level--or, more precisely with a directed hypergraph $\mathcal A$, which is the qualitative structure of a probabilistic dependency graph (PDG). When A represents a qualitative Bayesian network, QIM-compatibility with $\mathcal A$ reduces to satisfying the appropriate conditional independencies. But giving semantics to hypergraphs using QIM-compatibility lets us do much more. For one thing, we can capture functional dependencies. For another, we can capture important aspects of causality using compatibility: we can use compatibility to understand cyclic causal graphs, and to demonstrate structural compatibility, we must essentially produce a causal model. Finally, compatibility has deep connections to information theory. Applying compatibility to cyclic structures helps to clarify a longstanding conceptual issue in information theory.
CV-VAE: A Compatible Video VAE for Latent Generative Video Models
Spatio-temporal compression of videos, utilizing networks such as Variational Autoencoders (VAE), plays a crucial role in OpenAI's SORA and numerous other video generative models. For instance, many LLM-like video models learn the distribution of discrete tokens derived from 3D VAEs within the VQVAE framework, while most diffusion-based video models capture the distribution of continuous latent extracted by 2D VAEs without quantization. The temporal compression is simply realized by uniform frame sampling which results in unsmooth motion between consecutive frames. Currently, there lacks of a commonly used continuous video (3D) VAE for latent diffusion-based video models in the research community. Moreover, since current diffusion-based approaches are often implemented using pre-trained text-to-image (T2I) models, directly training a video VAE without considering the compatibility with existing T2I models will result in a latent space gap between them, which will take huge computational resources for training to bridge the gap even with the T2I models as initialization.