We introduce Concept Bottleneck Protein Language Models (CB-pLM), a generative masked language model with a layer where each neuron corresponds to an interpretable concept. Our architecture offers three key benefits: i) Control: We can intervene on concept values to precisely control the properties of generated proteins, achieving a 3$\times$ larger change in desired concept values compared to baselines. ii) Interpretability: A linear mapping between concept values and predicted tokens allows transparent analysis of the model's decision-making process. iii) Debugging: This transparency facilitates easy debugging of trained models. Our models achieve pre-training perplexity and downstream task performance comparable to traditional masked protein language models, demonstrating that interpretability does not compromise performance. While adaptable to any language model, we focus on masked protein language models due to their importance in drug discovery and the ability to validate our model's capabilities through real-world experiments and expert knowledge. We scale our CB-pLM from 24 million to 3 billion parameters, making them the largest Concept Bottleneck Models trained and the first capable of generative language modeling.

Generative modeling is increasingly important for data-driven computational design. Conventional approaches pair a generative model with a discriminative model to select or guide samples toward optimized designs. Yet discriminative models often struggle in data-scarce settings, common in scientific applications, and are unreliable in the tails of the distribution where optimal designs typically lie. We introduce generative property enhancer (GPE), an approach that implicitly guides generation by matching samples with lower property values to higher-value ones. Formulated as conditional density estimation, our framework defines a target distribution with improved properties, compelling the generative model to produce enhanced, diverse designs without auxiliary predictors. GPE is simple, scalable, end-to-end, modality-agnostic, and integrates seamlessly with diverse generative model architectures and losses. We demonstrate competitive empirical results on standard _in silico_ offline (non-sequential) protein fitness optimization benchmarks. Finally, we propose iterative training on a combination of limited real data and self-generated synthetic data, enabling extrapolation beyond the original property ranges.

We introduce a generative model with an intrinsically interpretable layer---a concept bottleneck layer---that constrains the model to encode human-understandable concepts. The concept bottleneck layer partitions the generative model into three parts: the pre-concept bottleneck portion, the CB layer, and the post-concept bottleneck portion. To train CB generative models, we complement the traditional task-based loss function for training generative models with a concept loss and an orthogonality loss. The CB layer and these loss terms are model agnostic, which we demonstrate by applying the CB layer to three different families of generative models: generative adversarial networks, variational autoencoders, and diffusion models. On multiple datasets across different types of generative models, steering a generative model, with the CB layer, outperforms all baselines---in some cases, it is \textit{10 times} more effective. In addition, we show how the CB layer can be used to interpret the output of the generative model and debug the model during or post training.

Saliency methods have been widely used to highlight important input features in model predictions. Most existing methods use backpropagation on a modified gradient function to generate saliency maps. Thus, noisy gradients can result in unfaithful feature attributions. In this paper, we tackle this issue and introduce a {\it saliency guided training} procedure for neural networks to reduce noisy gradients used in predictions while retaining the predictive performance of the model. Our saliency guided training procedure iteratively masks features with small and potentially noisy gradients while maximizing the similarity of model outputs for both masked and unmasked inputs. We apply the saliency guided training procedure to various synthetic and real data sets from computer vision, natural language processing, and time series across diverse neural architectures, including Recurrent Neural Networks, Convolutional Networks, and Transformers. Through qualitative and quantitative evaluations, we show that saliency guided training procedure significantly improves model interpretability across various domains while preserving its predictive performance.

Saliency methods are used extensively to highlight the importance of input features in model predictions. These methods are mostly used in vision and language tasks, and their applications to time series data is relatively unexplored. In this paper, we set out to extensively compare the performance of various saliency-based interpretability methods across diverse neural architectures, including Recurrent Neural Network, Temporal Convolutional Networks, and Transformers in a new benchmark of synthetic time series data. We propose and report multiple metrics to empirically evaluate the performance of saliency methods for detecting feature importance over time using both precision (i.e., whether identified features contain meaningful signals) and recall (i.e., the number of features with signal identified as important). Through several experiments, we show that (i) in general, network architectures and saliency methods fail to reliably and accurately identify feature importance over time in time series data, (ii) this failure is mainly due to the conflation of time and feature domains, and (iii) the quality of saliency maps can be improved substantially by using our proposed two-step temporal saliency rescaling (TSR) approach that first calculates the importance of each time step before calculating the importance of each feature at a time step.

Recent efforts to improve the interpretability of deep neural networks use saliency to characterize the importance of input features to predictions made by models. Work on interpretability using saliency-based methods on Recurrent Neural Networks (RNNs) has mostly targeted language tasks, and their applicability to time series data is less understood. In this work we analyze saliency-based methods for RNNs, both classical and gated cell architectures. We show that RNN saliency vanishes over time, biasing detection of salient features only to later time steps and are, therefore, incapable of reliably detecting important features at arbitrary time intervals. To address this vanishing saliency problem, we propose a novel RNN cell structure (input-cell attention), which can extend any RNN cell architecture. At each time step, instead of only looking at the current input vector, input-cell attention uses a fixed-size matrix embedding, each row of the matrix attending to different inputs from current or previous time steps. Using synthetic data, we show that the saliency map produced by the input-cell attention RNN is able to faithfully detect important features regardless of their occurrence in time. We also apply the input-cell attention RNN on a neuroscience task analyzing functional Magnetic Resonance Imaging (fMRI) data for human subjects performing a variety of tasks. In this case, we use saliency to characterize brain regions (input features) for which activity is important to distinguish between tasks. We show that standard RNN architectures are only capable of detecting important brain regions in the last few time steps of the fMRI data, while the input-cell attention model is able to detect important brain region activity across time without latter time step biases.