Michael M. Danziger

Yoel Shoshan, Moshiko Raboh, Michal Ozery-Flato et al.

Large language models applied to vast biological datasets have the potential to transform biology by uncovering disease mechanisms and accelerating drug development. However, current models are often siloed, trained separately on small-molecules, proteins, or transcriptomic data, limiting their ability to capture complex, multi-modal interactions. Effective drug discovery requires computational tools that integrate multiple biological entities while supporting prediction and generation, a challenge existing models struggle to address. For this purpose, we present MAMMAL - Molecular Aligned Multi-Modal Architecture and Language - a versatile method applied to create a multi-task foundation model that learns from large-scale biological datasets across diverse modalities, including proteins, small-molecules, and omics. MAMMAL's structured prompt syntax supports classification, regression, and generation tasks while handling token and scalar inputs and outputs. Evaluated on eleven diverse downstream tasks, it reaches a new state of the art (SOTA) in nine tasks and is comparable to SOTA in two tasks, all within a unified architecture, unlike prior task-specific models. Additionally, we explored Alphafold 3 binding prediction capabilities on antibody-antigen and nanobody-antigen complexes showing significantly better classification performance of MAMMAL in 3 out of 4 targets. The model code and pretrained weights are publicly available at https://github.com/BiomedSciAI/biomed-multi-alignment and https://huggingface.co/ibm/biomed.omics.bl.sm.ma-ted-458m

Bharath Dandala, Michael M. Danziger, Ella Barkan et al.

Transcriptomic foundation models (TFMs) have recently emerged as powerful tools for analyzing gene expression in cells and tissues, supporting key tasks such as cell-type annotation, batch correction, and perturbation prediction. However, the diversity of model implementations and training strategies across recent TFMs, though promising, makes it challenging to isolate the contribution of individual design choices or evaluate their potential synergies. This hinders the field's ability to converge on best practices and limits the reproducibility of insights across studies. We present BMFM-RNA, an open-source, modular software package that unifies diverse TFM pretraining and fine-tuning objectives within a single framework. Leveraging this capability, we introduce a novel training objective, whole cell expression decoder (WCED), which captures global expression patterns using an autoencoder-like CLS bottleneck representation. In this paper, we describe the framework, supported input representations, and training objectives. We evaluated four model checkpoints pretrained on CELLxGENE using combinations of masked language modeling (MLM), WCED and multitask learning. Using the benchmarking capabilities of BMFM-RNA, we show that WCED-based models achieve performance that matches or exceeds state-of-the-art approaches like scGPT across more than a dozen datasets in both zero-shot and fine-tuning tasks. BMFM-RNA, available as part of the biomed-multi-omics project ( https://github.com/BiomedSciAI/biomed-multi-omic ), offers a reproducible foundation for systematic benchmarking and community-driven exploration of optimal TFM training strategies, enabling the development of more effective tools to leverage the latest advances in AI for understanding cell biology.

Michael M. Danziger, Omkar R. Gojala, Sean P. Cornelius

Though robustness of networks to random attacks has been widely studied, intentional destruction by an intelligent agent is not tractable with previous methods. Here we devise a single-player game on a lattice that mimics the logic of an attacker attempting to destroy a network. The objective of the game is to disable all nodes in the fewest number of steps. We develop a reinforcement learning approach using deep Q-learning that is capable of learning to play this game successfully, and in so doing, to optimally attack a network. Because the learning algorithm is universal, we train agents on different definitions of robustness and compare the learned strategies. We find that superficially similar definitions of robustness induce different strategies in the trained agent, implying that optimally attacking or defending a network is sensitive the particular objective. Our method provides a new approach to understand network robustness, with potential applications to other discrete processes in disordered systems.

Sebastian M. Krause, Michael M. Danziger, Vinko Zlatić

Redundancy is commonly used to guarantee continued functionality in networked systems. However, often many nodes are vulnerable to the same failure or adversary. A "backup" path is not sufficient if both paths depend on nodes which share a vulnerability.For example, if two nodes of the Internet cannot be connected without using routers belonging to a given untrusted entity, then all of their communication-regardless of the specific paths utilized-will be intercepted by the controlling entity.In this and many other cases, the vulnerabilities affecting the network are disjoint: each node has exactly one vulnerability but the same vulnerability can affect many nodes. To discover optimal redundancy in this scenario, we describe each vulnerability as a color and develop a "color-avoiding percolation" which uncovers a hidden color-avoiding connectivity. We present algorithms for color-avoiding percolation of general networks and an analytic theory for random graphs with uniformly distributed colors including critical phenomena. We demonstrate our theory by uncovering the hidden color-avoiding connectivity of the Internet. We find that less well-connected countries are more likely able to communicate securely through optimally redundant paths than highly connected countries like the US. Our results reveal a new layer of hidden structure in complex systems and can enhance security and robustness through optimal redundancy in a wide range of systems including biological, economic and communications networks.