Self-supervised training of language models (LMs) has seen great success for protein sequences in learning meaningful representations and for generative drug design. Most protein LMs are based on the Transformer architecture trained on individual proteins with short context lengths. Such protein LMs cannot extrapolate to longer proteins and protein complexes well. They also fail to account for the underlying biological mechanisms carried out by biomolecular interactions and dynamics i.e., proteins often interact with other proteins, molecules, and pathways in complex biological systems. In this work, we propose LC-PLM based on an alternative protein LM architecture, BiMamba-S, built off selective structured state-space models, to learn high-quality universal protein representations at the amino acid token level using masked language modeling. We also introduce its graph-contextual variant, LC-PLM-G, which contextualizes protein-protein interaction (PPI) graphs for a second stage of training. LC-PLM demonstrates favorable neural scaling laws, better length extrapolation capability, and a 7% to 34% improvement on protein downstream tasks than Transformer-based ESM-2. LC-PLM-G further trained within the context of PPI graphs shows promising results on protein structure and function prediction tasks. Our study demonstrates the benefit of increasing the context size with computationally efficient LM architecture (e.g. structured state space models) in learning universal protein representations and incorporating molecular interaction context contained in biological graphs.

The ability to form, retrieve, and reason about memories in response to stimuli serves as the cornerstone for general intelligence - shaping entities capable of learning, adaptation, and intuitive insight. Large Language Models (LLMs) have proven their ability, given the proper memories or context, to reason and respond meaningfully to stimuli. However, they are still unable to optimally encode, store, and retrieve memories - the ability to do this would unlock their full ability to operate as AI agents, and to specialize to niche domains. To remedy this, one promising area of research is Retrieval Augmented Generation (RAG), which aims to augment LLMs by providing them with rich in-context examples and information. In question-answering (QA) applications, RAG methods embed the text of interest in chunks, and retrieve the most relevant chunks for a prompt using text embeddings. Motivated by human memory encoding and retrieval, we aim to improve over standard RAG methods by generating and encoding higher-level information and tagging the chunks by their utility to answer questions. We introduce Graphical Eigen Memories For Retrieval Augmented Generation (GEM-RAG). GEM-RAG works by tagging each chunk of text in a given text corpus with LLM generated ``utility'' questions, connecting chunks in a graph based on the similarity of both their text and utility questions, and then using the eigendecomposition of the memory graph to build higher level summary nodes that capture the main themes of the text. We evaluate GEM-RAG, using both UnifiedQA and GPT-3.5 Turbo as the LLMs, with SBERT, and OpenAI's text encoders on two standard QA tasks, showing that GEM-RAG outperforms other state-of-the-art RAG methods on these tasks. We also discuss the implications of having a robust RAG system and future directions.

We propose denoising diffusion variational inference (DDVI), an approximate inference algorithm for latent variable models which relies on diffusion models as expressive variational posteriors. Our method augments variational posteriors with auxiliary latents, which yields an expressive class of models that perform diffusion in latent space by reversing a user-specified noising process. We fit these models by optimizing a novel lower bound on the marginal likelihood inspired by the wake-sleep algorithm. Our method is easy to implement (it fits a regularized extension of the ELBO), is compatible with black-box variational inference, and outperforms alternative classes of approximate posteriors based on normalizing flows or adversarial networks. When applied to deep latent variable models, our method yields the denoising diffusion VAE (DD-VAE) algorithm. We use this algorithm on a motivating task in biology--inferring latent ancestry from human genomes--outperforming strong baselines on the Thousand Genomes dataset. Latent variable methods often rely on variational inference to fit an approximate model of the posterior distribution (Vahdat & Kautz, 2020; Maaløe et al., 2016). The expressivity of this model has a significant impact on the performance of variational inference (Kingma et al., 2016), which motivates research that leverages modern generative models--including normalizing flows (Rezende & Mohamed, 2015) and generative adversarial networks (Goodfellow et al., 2014; Makhzani et al., 2015)--to represent expressive approximate posteriors.

We propose a memory-efficient finetuning algorithm for large language models (LLMs) that supports finetuning LLMs with 65B parameters in 3-bit or 4-bit precision on as little as one 48GB GPU. Our method, modular low-rank adaptation (ModuLoRA), integrates any user-specified weight quantizer with finetuning via low-rank adapters (LoRAs). Our approach relies on a simple quantization-agnostic backward pass that adaptively materializes low-precision LLM weights from a custom black-box quantization module. This approach enables finetuning 3-bit LLMs for the first time--leveraging state-of-the-art 3-bit OPTQ quantization often outperforms finetuning that relies on less sophisticated 4-bit and 8-bit methods. In our experiments, ModuLoRA attains competitive performance on text classification, natural language infernece, and instruction following tasks using significantly less memory than existing approaches, and we also surpass the state-of-the-art ROUGE score on a popular summarization task. We release ModuLoRA together with a series of low-precision models--including the first family of 3-bit instruction following Alpaca LLMs--as part of LLMTOOLS, a user-friendly library for quantizing, running, and finetuning LLMs on consumer GPUs.

While diffusion models excel at generating high-quality samples, their latent variables typically lack semantic meaning and are not suitable for representation learning. Here, we propose InfoDiffusion, an algorithm that augments diffusion models with low-dimensional latent variables that capture high-level factors of variation in the data. InfoDiffusion relies on a learning objective regularized with the mutual information between observed and hidden variables, which improves latent space quality and prevents the latents from being ignored by expressive diffusion-based decoders. Empirically, we find that InfoDiffusion learns disentangled and human-interpretable latent representations that are competitive with state-of-the-art generative and contrastive methods, while retaining the high sample quality of diffusion models. Our method enables manipulating the attributes of generated images and has the potential to assist tasks that require exploring a learned latent space to generate quality samples, e.g., generative design.

We introduce M$^2$Hub, a toolkit for advancing machine learning in materials discovery. Machine learning has achieved remarkable progress in modeling molecular structures, especially biomolecules for drug discovery. However, the development of machine learning approaches for modeling materials structures lag behind, which is partly due to the lack of an integrated platform that enables access to diverse tasks for materials discovery. To bridge this gap, M$^2$Hub will enable easy access to materials discovery tasks, datasets, machine learning methods, evaluations, and benchmark results that cover the entire workflow. Specifically, the first release of M$^2$Hub focuses on three key stages in materials discovery: virtual screening, inverse design, and molecular simulation, including 9 datasets that covers 6 types of materials with 56 tasks across 8 types of material properties. We further provide 2 synthetic datasets for the purpose of generative tasks on materials. In addition to random data splits, we also provide 3 additional data partitions to reflect the real-world materials discovery scenarios. State-of-the-art machine learning methods (including those are suitable for materials structures but never compared in the literature) are benchmarked on representative tasks. Our codes and library are publicly available at https://github.com/yuanqidu/M2Hub.

Accurate prediction of the protein-ligand binding affinities is an essential challenge in the structure-based drug design. Despite recent advance in data-driven methods in affinity prediction, their accuracy is still limited, partially because they only take advantage of static crystal structures while the actual binding affinities are generally depicted by the thermodynamic ensembles between proteins and ligands. One effective way to approximate such a thermodynamic ensemble is to use molecular dynamics (MD) simulation. Here, we curated an MD dataset containing 3,218 different protein-ligand complexes, and further developed Dynaformer, which is a graph-based deep learning model. Dynaformer was able to accurately predict the binding affinities by learning the geometric characteristics of the protein-ligand interactions from the MD trajectories. In silico experiments demonstrated that our model exhibits state-of-the-art scoring and ranking power on the CASF-2016 benchmark dataset, outperforming the methods hitherto reported. Moreover, we performed a virtual screening on the heat shock protein 90 (HSP90) using Dynaformer that identified 20 candidates and further experimentally validated their binding affinities. We demonstrated that our approach is more efficient, which can identify 12 hit compounds (two were in the submicromolar range), including several newly discovered scaffolds. We anticipate this new synergy between large-scale MD datasets and deep learning models will provide a new route toward accelerating the early drug discovery process.

Various contrastive learning approaches have been proposed in recent years and achieve significant empirical success. While effective and prevalent, contrastive learning has been less explored for time series data. A key component of contrastive learning is to select appropriate augmentations imposing some priors to construct feasible positive samples, such that an encoder can be trained to learn robust and discriminative representations. Unlike image and language domains where ``desired'' augmented samples can be generated with the rule of thumb guided by prefabricated human priors, the ad-hoc manual selection of time series augmentations is hindered by their diverse and human-unrecognizable temporal structures. How to find the desired augmentations of time series data that are meaningful for given contrastive learning tasks and datasets remains an open question. In this work, we address the problem by encouraging both high \textit{fidelity} and \textit{variety} based upon information theory. A theoretical analysis leads to the criteria for selecting feasible data augmentations. On top of that, we propose a new contrastive learning approach with information-aware augmentations, InfoTS, that adaptively selects optimal augmentations for time series representation learning. Experiments on various datasets show highly competitive performance with up to 12.0\% reduction in MSE on forecasting tasks and up to 3.7\% relative improvement in accuracy on classification tasks over the leading baselines.

Modern machine learning techniques have been extensively applied to materials science, especially for property prediction tasks. A majority of these methods address scalar property predictions, while more challenging spectral properties remain less emphasized. We formulate a crystal-to-sequence learning task and propose a novel attention-based learning method, Xtal2DoS, which decodes the sequential representation of the material density of states (DoS) properties by incorporating the learned atomic embeddings through attention networks. Experiments show Xtal2DoS is faster than the existing models, and consistently outperforms other state-of-the-art methods on four metrics for two fundamental spectral properties, phonon and electronic DoS.

Data augmentation has recently seen increased interest in graph machine learning given its demonstrated ability to improve model performance and generalization by added training data. Despite this recent surge, the area is still relatively under-explored, due to the challenges brought by complex, non-Euclidean structure of graph data, which limits the direct analogizing of traditional augmentation operations on other types of image, video or text data. Our work aims to give a necessary and timely overview of existing graph data augmentation methods; notably, we present a comprehensive and systematic survey of graph data augmentation approaches, summarizing the literature in a structured manner. We first introduce three different taxonomies for categorizing graph data augmentation methods from the data, task, and learning perspectives, respectively. Next, we introduce recent advances in graph data augmentation, differentiated by their methodologies and applications. We conclude by outlining currently unsolved challenges and directions for future research. Overall, our work aims to clarify the landscape of existing literature in graph data augmentation and motivates additional work in this area, providing a helpful resource for researchers and practitioners in the broader graph machine learning domain. Additionally, we provide a continuously updated reading list at https://github.com/zhao-tong/graph-data-augmentation-papers.