Micha Livne

Micha Livne, Zulfat Miftahutdinov, Elena Tutubalina et al.

Large Language Models (LLMs) have substantially driven scientific progress in various domains, and many papers have demonstrated their ability to tackle complex problems with creative solutions. Our paper introduces a new foundation model, nach0, capable of solving various chemical and biological tasks: biomedical question answering, named entity recognition, molecular generation, molecular synthesis, attributes prediction, and others. nach0 is a multi-domain and multi-task encoder-decoder LLM pre-trained on unlabeled text from scientific literature, patents, and molecule strings to incorporate a range of chemical and linguistic knowledge. We employed instruction tuning, where specific task-related instructions are utilized to fine-tune nach0 for the final set of tasks. To train nach0 effectively, we leverage the NeMo framework, enabling efficient parallel optimization of both base and large model versions. Extensive experiments demonstrate that our model outperforms state-of-the-art baselines on single-domain and cross-domain tasks. Furthermore, it can generate high-quality outputs in molecular and textual formats, showcasing its effectiveness in multi-domain setups.

Danny Reidenbach, Micha Livne, Rajesh K. Ilango et al.

We address the task of controlled generation of small molecules, which entails finding novel molecules with desired properties under certain constraints (e.g., similarity to a reference molecule). Here we introduce MolMIM, a probabilistic auto-encoder for small molecule drug discovery that learns an informative and clustered latent space. MolMIM is trained with Mutual Information Machine (MIM) learning, and provides a fixed length representation of variable length SMILES strings. Since encoder-decoder models can learn representations with ``holes'' of invalid samples, here we propose a novel extension to the training procedure which promotes a dense latent space, and allows the model to sample valid molecules from random perturbations of latent codes. We provide a thorough comparison of MolMIM to several variable-size and fixed-size encoder-decoder models, demonstrating MolMIM's superior generation as measured in terms of validity, uniqueness, and novelty. We then utilize CMA-ES, a naive black-box and gradient free search algorithm, over MolMIM's latent space for the task of property guided molecule optimization. We achieve state-of-the-art results in several constrained single property optimization tasks as well as in the challenging task of multi-objective optimization, improving over previous success rate SOTA by more than 5\% . We attribute the strong results to MolMIM's latent representation which clusters similar molecules in the latent space, whereas CMA-ES is often used as a baseline optimization method. We also demonstrate MolMIM to be favourable in a compute limited regime, making it an attractive model for such cases.

Peter St. John, Dejun Lin, Polina Binder et al.

Artificial Intelligence models encoding biology and chemistry are opening new routes to high-throughput and high-quality in-silico drug development. However, their training increasingly relies on computational scale, with recent protein language models (pLM) training on hundreds of graphical processing units (GPUs). We introduce the BioNeMo Framework to facilitate the training of computational biology and chemistry AI models across hundreds of GPUs. Its modular design allows the integration of individual components, such as data loaders, into existing workflows and is open to community contributions. We detail technical features of the BioNeMo Framework through use cases such as pLM pre-training and fine-tuning. On 256 NVIDIA A100s, BioNeMo Framework trains a three billion parameter BERT-based pLM on over one trillion tokens in 4.2 days. The BioNeMo Framework is open-source and free for everyone to use.

Micha Livne

Learning representations that transfer well to diverse downstream tasks remains a central challenge in representation learning. Existing paradigms -- contrastive learning, self-supervised masking, and denoising auto-encoders -- balance this challenge with different trade-offs. We introduce the {contrastive Mutual Information Machine} (cMIM), a probabilistic framework that extends the Mutual Information Machine (MIM) with a contrastive objective. While MIM maximizes mutual information between inputs and latents and promotes clustering of codes, it falls short on discriminative tasks. cMIM addresses this gap by imposing global discriminative structure while retaining MIM's generative fidelity. Our contributions are threefold. First, we propose cMIM, a contrastive extension of MIM that removes the need for positive data augmentation and is substantially less sensitive to batch size than InfoNCE. Second, we introduce {informative embeddings}, a general technique for extracting enriched features from encoder-decoder models that boosts discriminative performance without additional training and applies broadly beyond MIM. Third, we provide empirical evidence across vision and molecular benchmarks showing that cMIM outperforms MIM and InfoNCE on classification and regression tasks while preserving competitive reconstruction quality. These results position cMIM as a unified framework for representation learning, advancing the goal of models that serve both discriminative and generative applications effectively.

Micha Livne

Learning representations that generalize well to unknown downstream tasks is a central challenge in representation learning. Existing approaches such as contrastive learning, self-supervised masking, and denoising auto-encoders address this challenge with varying trade-offs. In this paper, we introduce the {contrastive Mutual Information Machine} (cMIM), a probabilistic framework that augments the Mutual Information Machine (MIM) with a novel contrastive objective. While MIM maximizes mutual information between inputs and latent variables and encourages clustering of latent codes, its representations underperform on discriminative tasks compared to state-of-the-art alternatives. cMIM addresses this limitation by enforcing global discriminative structure while retaining MIM's generative strengths. We present two main contributions: (1) we propose cMIM, a contrastive extension of MIM that eliminates the need for positive data augmentation and is robust to batch size, unlike InfoNCE-based methods; (2) we introduce {informative embeddings}, a general technique for extracting enriched representations from encoder--decoder models that substantially improve discriminative performance without additional training, and which apply broadly beyond MIM. Empirical results demonstrate that cMIM consistently outperforms MIM and InfoNCE in classification and regression tasks, while preserving comparable reconstruction quality. These findings suggest that cMIM provides a unified framework for learning representations that are simultaneously effective for discriminative and generative applications.

Micha Livne, Kevin Swersky, David J. Fleet

SentenceMIM is a probabilistic auto-encoder for language data, trained with Mutual Information Machine (MIM) learning to provide a fixed length representation of variable length language observations (i.e., similar to VAE). Previous attempts to learn VAEs for language data faced challenges due to posterior collapse. MIM learning encourages high mutual information between observations and latent variables, and is robust against posterior collapse. As such, it learns informative representations whose dimension can be an order of magnitude higher than existing language VAEs. Importantly, the SentenceMIM loss has no hyper-parameters, simplifying optimization. We compare sentenceMIM with VAE, and AE on multiple datasets. SentenceMIM yields excellent reconstruction, comparable to AEs, with a rich structured latent space, comparable to VAEs. The structured latent representation is demonstrated with interpolation between sentences of different lengths. We demonstrate the versatility of sentenceMIM by utilizing a trained model for question-answering and transfer learning, without fine-tuning, outperforming VAE and AE with similar architectures.

Micha Livne, Kevin Swersky, David J. Fleet

We introduce the Mutual Information Machine (MIM), a probabilistic auto-encoder for learning joint distributions over observations and latent variables. MIM reflects three design principles: 1) low divergence, to encourage the encoder and decoder to learn consistent factorizations of the same underlying distribution; 2) high mutual information, to encourage an informative relation between data and latent variables; and 3) low marginal entropy, or compression, which tends to encourage clustered latent representations. We show that a combination of the Jensen-Shannon divergence and the joint entropy of the encoding and decoding distributions satisfies these criteria, and admits a tractable cross-entropy bound that can be optimized directly with Monte Carlo and stochastic gradient descent. We contrast MIM learning with maximum likelihood and VAEs. Experiments show that MIM learns representations with high mutual information, consistent encoding and decoding distributions, effective latent clustering, and data log likelihood comparable to VAE, while avoiding posterior collapse.

Micha Livne, Kevin Swersky, David J. Fleet

We introduce the Mutual Information Machine (MIM), a novel formulation of representation learning, using a joint distribution over the observations and latent state in an encoder/decoder framework. Our key principles are symmetry and mutual information, where symmetry encourages the encoder and decoder to learn different factorizations of the same underlying distribution, and mutual information, to encourage the learning of useful representations for downstream tasks. Our starting point is the symmetric Jensen-Shannon divergence between the encoding and decoding joint distributions, plus a mutual information encouraging regularizer. We show that this can be bounded by a tractable cross entropy loss function between the true model and a parameterized approximation, and relate this to the maximum likelihood framework. We also relate MIM to variational autoencoders (VAEs) and demonstrate that MIM is capable of learning symmetric factorizations, with high mutual information that avoids posterior collapse.

Micha Livne, David Fleet

We formulate a new class of conditional generative models based on probability flows. Trained with maximum likelihood, it provides efficient inference and sampling from class-conditionals or the joint distribution, and does not require a priori knowledge of the number of classes or the relationships between classes. This allows one to train generative models from multiple, heterogeneous datasets, while retaining strong prior models over subsets of the data (e.g., from a single dataset, class label, or attribute). In this paper, in addition to end-to-end learning, we show how one can learn a single model from multiple datasets with a relatively weak Glow architecture, and then extend it by conditioning on different knowledge types (e.g., a single dataset). This yields log likelihood comparable to state-of-the-art, compelling samples from conditional priors.

Micha Livne, Leonid Sigal, Marcus A. Brubaker et al.

We propose a generative approach to physics-based motion capture. Unlike prior attempts to incorporate physics into tracking that assume the subject and scene geometry are calibrated and known a priori, our approach is automatic and online. This distinction is important since calibration of the environment is often difficult, especially for motions with props, uneven surfaces, or outdoor scenes. The use of physics in this context provides a natural framework to reason about contact and the plausibility of recovered motions. We propose a fast data-driven parametric body model, based on linear-blend skinning, which decouples deformations due to pose, anthropometrics and body shape. Pose (and shape) parameters are estimated using robust ICP optimization with physics-based dynamic priors that incorporate contact. Contact is estimated from torque trajectories and predictions of which contact points were active. To our knowledge, this is the first approach to take physics into account without explicit {\em a priori} knowledge of the environment or body dimensions. We demonstrate effective tracking from a noisy single depth camera, improving on state-of-the-art results quantitatively and producing better qualitative results, reducing visual artifacts like foot-skate and jitter.

Micha Livne, David J. Fleet

We introduce TzK (pronounced "task"), a conditional probability flow-based model that exploits attributes (e.g., style, class membership, or other side information) in order to learn tight conditional prior around manifolds of the target observations. The model is trained via approximated ML, and offers efficient approximation of arbitrary data sample distributions (similar to GAN and flow-based ML), and stable training (similar to VAE and ML), while avoiding variational approximations. TzK exploits meta-data to facilitate a bottleneck, similar to autoencoders, thereby producing a low-dimensional representation. Unlike autoencoders, the bottleneck does not limit model expressiveness, similar to flow-based ML. Supervised, unsupervised, and semi-supervised learning are supported by replacing missing observations with samples from learned priors. We demonstrate TzK by training jointly on MNIST and Omniglot datasets with minimal preprocessing, and weak supervision, with results comparable to state-of-the-art.