Lindsay Edwards

Paul Scherer, Alison Pouplin, Alice Del Vecchio et al.

Active learning (AL) is a sub-field of ML focused on the development of methods to iteratively and economically acquire data by strategically querying new data points that are the most useful for a particular task. Here, we introduce PyRelationAL, an open source library for AL research. We describe a modular toolkit based around a two step design methodology for composing pool-based active learning strategies applicable to both single-acquisition and batch-acquisition strategies. This framework allows for the mathematical and practical specification of a broad number of existing and novel strategies under a consistent programming model and abstraction. Furthermore, we incorporate datasets and active learning tasks applicable to them to simplify comparative evaluation and benchmarking, along with an initial group of benchmarks across datasets included in this library. The toolkit is compatible with existing ML frameworks. PyRelationAL is maintained using modern software engineering practices -- with an inclusive contributor code of conduct -- to promote long term library quality and utilisation. PyRelationAL is available under a permissive Apache licence on PyPi and at https://github.com/RelationRx/pyrelational.

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.

Thomas Gaudelet, Alice Del Vecchio, Eli M Carrami et al.

Interventions play a pivotal role in the study of complex biological systems. In drug discovery, genetic interventions (such as CRISPR base editing) have become central to both identifying potential therapeutic targets and understanding a drug's mechanism of action. With the advancement of CRISPR and the proliferation of genome-scale analyses such as transcriptomics, a new challenge is to navigate the vast combinatorial space of concurrent genetic interventions. Addressing this, our work concentrates on estimating the effects of pairwise genetic combinations on the cellular transcriptome. We introduce two novel contributions: Salt, a biologically-inspired baseline that posits the mostly additive nature of combination effects, and Peper, a deep learning model that extends Salt's additive assumption to achieve unprecedented accuracy. Our comprehensive comparison against existing state-of-the-art methods, grounded in diverse metrics, and our out-of-distribution analysis highlight the limitations of current models in realistic settings. This analysis underscores the necessity for improved modelling techniques and data acquisition strategies, paving the way for more effective exploration of genetic intervention effects.

Luka Kovačević, Thomas Gaudelet, James Opzoomer et al.

Despite substantial efforts, deep learning has not yet delivered a transformative impact on elucidating regulatory biology, particularly in the realm of predicting gene expression profiles. Here, we argue that genuine "foundation models" of regulatory biology will remain out of reach unless guided by frameworks that integrate mechanistic insight with principled experimental design. We present one such ground-up, semi-mechanistic framework that unifies perturbation-based experimental designs across both in vitro and in vivo CRISPR screens, accounting for differentiating and non-differentiating cellular systems. By revealing previously unrecognised assumptions in published machine learning methods, our approach clarifies links with popular techniques such as variational autoencoders and structural causal models. In practice, this framework suggests a modified loss function that we demonstrate can improve predictive performance, and further suggests an error analysis that informs batching strategies. Ultimately, since cellular regulation emerges from innumerable interactions amongst largely uncharted molecular components, we contend that systems-level understanding cannot be achieved through structural biology alone. Instead, we argue that real progress will require a first-principles perspective on how experiments capture biological phenomena, how data are generated, and how these processes can be reflected in more faithful modelling architectures.

Talip Ucar, Ehsan Hajiramezanali, Lindsay Edwards

Self-supervised learning has been shown to be very effective in learning useful representations, and yet much of the success is achieved in data types such as images, audio, and text. The success is mainly enabled by taking advantage of spatial, temporal, or semantic structure in the data through augmentation. However, such structure may not exist in tabular datasets commonly used in fields such as healthcare, making it difficult to design an effective augmentation method, and hindering a similar progress in tabular data setting. In this paper, we introduce a new framework, Subsetting features of Tabular data (SubTab), that turns the task of learning from tabular data into a multi-view representation learning problem by dividing the input features to multiple subsets. We argue that reconstructing the data from the subset of its features rather than its corrupted version in an autoencoder setting can better capture its underlying latent representation. In this framework, the joint representation can be expressed as the aggregate of latent variables of the subsets at test time, which we refer to as collaborative inference. Our experiments show that the SubTab achieves the state of the art (SOTA) performance of 98.31% on MNIST in tabular setting, on par with CNN-based SOTA models, and surpasses existing baselines on three other real-world datasets by a significant margin.