Convolutional Neural Networks have demonstrated dermatologist-level performance in the classification of melanoma from skin lesion images, but prediction irregularities due to biases seen within the training data are an issue that should be addressed before widespread deployment is possible. In this work, we robustly remove bias and spurious variation from an automated melanoma classification pipeline using two leading bias unlearning techniques. We show that the biases introduced by surgical markings and rulers presented in previous studies can be reasonably mitigated using these bias removal methods. We also demonstrate the generalisation benefits of unlearning spurious variation relating to the imaging instrument used to capture lesion images. Our experimental results provide evidence that the effects of each of the aforementioned biases are notably reduced, with different debiasing techniques excelling at different tasks.

A popular approach to reduce the size of a massive dataset is to apply efficient online sampling to the stream of data as it is read or generated. Online sampling routines are currently restricted to variations of reservoir sampling, where each sample is selected uniformly and independently of other samples. This renders them unsuitable for large-scale applications in computational biology, such as metagenomic community profiling and protein function annotation, which suffer from severe class imbalance. To maintain a representative and diverse sample, we must identify and preferentially select data that are likely to belong to rare classes. We argue that existing schemes for diversity sampling have prohibitive overhead for large-scale problems and high-throughput streams. We propose an efficient sampling routine that uses an online representation of the data distribution as a prefilter to retain elements from rare groups. We apply this method to several genomic data analysis tasks and demonstrate significant speedup in downstream analysis without sacrificing the quality of the results. Because our algorithm is 2x faster and uses 1000x less memory than coreset, reservoir and sketch-based alternatives, we anticipate that it will become a useful preprocessing step for applications with large-scale streaming data.

How to properly model the inter-frame relation within the video sequence is an important but unsolved challenge for video restoration (VR). In this work, we propose an unsupervised flow-aligned sequence-to-sequence model (S2SVR) to address this problem. On the one hand, the sequence-to-sequence model, which has proven capable of sequence modeling in the field of natural language processing, is explored for the first time in VR. Optimized serialization modeling shows potential in capturing long-range dependencies among frames. On the other hand, we equip the sequence-to-sequence model with an unsupervised optical flow estimator to maximize its potential. The flow estimator is trained with our proposed unsupervised distillation loss, which can alleviate the data discrepancy and inaccurate degraded optical flow issues of previous flow-based methods. With reliable optical flow, we can establish accurate correspondence among multiple frames, narrowing the domain difference between 1D language and 2D misaligned frames and improving the potential of the sequence-to-sequence model. S2SVR shows superior performance in multiple VR tasks, including video deblurring, video super-resolution, and compressed video quality enhancement. https://github.com/linjing7/VR-Baseline

Electrocardiogram (ECG) is a widely used non-invasive diagnostic tool for heart diseases. Many studies have devised ECG analysis models (e.g., classifiers) to assist diagnosis. As an upstream task, researches have built generative models to synthesize ECG data, which are beneficial to providing training samples, privacy protection, and annotation reduction. However, previous generative methods for ECG often neither synthesized multi-view data, nor dealt with heart disease conditions. In this paper, we propose a novel disease-aware generative adversarial network for multi-view ECG synthesis called ME-GAN, which attains panoptic electrocardio representations conditioned on heart diseases and projects the representations onto multiple standard views to yield ECG signals. Since ECG manifestations of heart diseases are often localized in specific waveforms, we propose a new "mixup normalization" to inject disease information precisely into suitable locations. In addition, we propose a "view discriminator" to revert disordered ECG views into a pre-determined order, supervising the generator to obtain ECG representing correct view characteristics. Besides, a new metric, rFID, is presented to assess the quality of the synthesized ECG signals. Comprehensive experiments verify that our ME-GAN performs well on multi-view ECG signal synthesis with trusty morbid manifestations.

A key problem in computational biology is discovering the gene expression changes that regulate cell fate transitions, in which one cell type turns into another. However, each individual cell cannot be tracked longitudinally, and cells at the same point in real time may be at different stages of the transition process. This can be viewed as a problem of learning the behavior of a dynamical system from observations whose times are unknown. Additionally, a single progenitor cell type often bifurcates into multiple child cell types, further complicating the problem of modeling the dynamics. To address this problem, we developed an approach called variational mixtures of ordinary differential equations. By using a simple family of ODEs informed by the biochemistry of gene expression to constrain the likelihood of a deep generative model, we can simultaneously infer the latent time and latent state of each cell and predict its future gene expression state. The model can be interpreted as a mixture of ODEs whose parameters vary continuously across a latent space of cell states. Our approach dramatically improves data fit, latent time inference, and future cell state estimation of single-cell gene expression data compared to previous approaches.

In this work we investigate and demonstrate benefits of a Bayesian approach to imitation learning from multiple sensor inputs, as applied to the taskof opening office doors with a mobile manipulator. Augmenting policies with additional sensor inputs—such as RGB + depth cameras—is a straightforward approach to improving robot perception capabilities, especially for tasks that mayfavor different sensors in different situations. As we scale multi-sensor robotic learning to unstructured real-world settings (e.g. offices, homes) and more complex robot behaviors, we also increase reliance on simulators for cost, efficiency, andsafety. Consequently, the sim-to-real gap across multiple sensor modalities also increases, making simulated validation more difficult. We show that using the Variational Information Bottleneck (Alemi et al., 2016) to regularize convolutionalneural networks improves generalization to heldout domains and reduces the sim-to-real gap in a sensor-agnostic manner. As a side effect, thelearned embeddings also provide useful estimates of model uncertainty for each sensor. We demonstrate that our method is able to help close the sim-to-real gap and successfully fuse RGB and depth modalities based on understanding of thesituational uncertainty of each sensor. In a real-world office environment, we achieve 96% task success, improving upon the baseline by +16%.

Tandem mass spectrometry is the only high-throughput method for analyzing the protein content of complex biological samples and is thus the primary technology driving the growth of the field of proteomics. A key outstanding challenge in this field involves identifying the sequence of amino acids -the peptide- responsible for generating each observed spectrum, without making use of prior knowledge in the form of a peptide sequence database. Although various machine learning methods have been developed to address this de novo sequencing problem, challenges that arise when modeling tandem mass spectra have led to complex models that combine multiple neural networks and post-processing steps. We propose a simple yet powerful method for de novo peptide sequencing, Casanovo, that uses a transformer framework to map directly from a sequence of observed peaks (a mass spectrum) to a sequence of amino acids (a peptide). Our experiments show that Casanovo achieves state-of-the-art performance on a benchmark dataset using a standard cross-species evaluation framework which involves testing with spectra with never-before-seen peptide labels. Casanovo not only achieves superior performance but does so at a fraction of the model complexity and inference time required by other methods.

We consider the problem of predicting a protein sequence from its backbone atom coordinates. Machine learning approaches to this problem to date have been limited by the number of available experimentally determined protein structures. We augment training data by nearly three orders of magnitude by predicting structures for 12M protein sequences using AlphaFold2. Trained with this additional data, a sequence-to-sequence transformer with invariant geometric input processing layers achieves 51% native sequence recovery on structurally held-out backbones with 72% recovery for buried residues, an overall improvement of almost 10 percentage points over existing methods. The model generalizes to a variety of more complex tasks including design of protein complexes, partially masked structures, binding interfaces, and multiple states.

We propose Guided-TTS, a high-quality text-to-speech (TTS) model that does not require any transcript of target speaker using classifier guidance. Guided-TTS combines an unconditional diffusion probabilistic model with a separately trained phoneme classifier for classifier guidance. Our unconditional diffusion model learns to generate speech without any context from untranscribed speech data. For TTS synthesis, we guide the generative process of the diffusion model with a phoneme classifier trained on a large-scale speech recognition dataset. We present a norm-based scaling method that reduces the pronunciation errors of classifier guidance in Guided-TTS. We show that Guided-TTS achieves a performance comparable to that of the state-of-the-art TTS model, Grad-TTS, without any transcript for LJSpeech. We further demonstrate that Guided-TTS performs well on diverse datasets including a long-form untranscribed dataset.

In object detection, the detection backbone consumes more than half of the overall inference cost. Recent researches attempt to reduce this cost by optimizing the backbone architecture with the help of Neural Architecture Search (NAS). However, existing NAS methods for object detection require hundreds to thousands of GPU hours of searching, making them impractical in fast-paced research and development. In this work, we propose a novel zero-shot NAS method to address this issue. The proposed method, named MAE-DET, automatically designs efficient detection backbones via the Maximum Entropy Principle without training network parameters, reducing the architecture design cost to nearly zero yet delivering the state-of-the-art (SOTA) performance. Under the hood, MAE-DET maximizes the differential entropy of detection backbones, leading to a better feature extractor for object detection under the same computational budgets. After merely one GPU day of fully automatic design, MAE-DET innovates SOTA detection backbones on multiple detection benchmark datasets with little human intervention. Comparing to ResNet-50 backbone, MAE-DET is $+2.0\%$ better in mAP when using the same amount of FLOPs/parameters, and is $1.54$ times faster on NVIDIA V100 at the same mAP. Code and pre-trained models are available here (https://github.com/alibaba/lightweight-neural-architecture-search).

Designing protein sequences with a particular biological function is a long-lasting challenge for protein engineering. Recent advances in machine-learning-guided approaches focus on building a surrogate sequence-function model to reduce the burden of expensive in-lab experiments. In this paper, we study the exploration mechanism of model-guided sequence design. We leverage a natural property of protein fitness landscape that a concise set of mutations upon the wild-type sequence are usually sufficient to enhance the desired function. By utilizing this property, we propose Proximal Exploration (PEX) algorithm that prioritizes the evolutionary search for high-fitness mutants with low mutation counts. In addition, we develop a specialized model architecture, called Mutation Factorization Network (MuFacNet), to predict low-order mutational effects, which further improves the sample efficiency of model-guided evolution. In experiments, we extensively evaluate our method on a suite of in-silico protein sequence design tasks and demonstrate substantial improvement over baseline algorithms.

The ability to accurately model the fitness landscape of protein sequences is critical to a wide range of applications, from quantifying the effects of human variants on disease likelihood, to predicting immune-escape mutations in viruses and designing novel biotherapeutic proteins. Deep generative models of protein sequences trained on multiple sequence alignments have been the most successful approaches so far to address these tasks. The performance of these methods is however contingent on the availability of sufficiently deep and diverse alignments for reliable training. Their potential scope is thus limited by the fact many protein families are hard, if not impossible, to align. Large language models trained on massive quantities of non-aligned protein sequences from diverse families address these problems and show potential to eventually bridge the performance gap. We introduce Tranception, a novel transformer architecture leveraging autoregressive predictions and retrieval of homologous sequences at inference to achieve state-of-the-art fitness prediction performance. Given its markedly higher performance on multiple mutants, robustness to shallow alignments and ability to score indels, our approach offers significant gain of scope over existing approaches. To enable more rigorous model testing across a broader range of protein families, we develop ProteinGym -- an extensive set of multiplexed assays of variant effects, substantially increasing both the number and diversity of assays compared to existing benchmarks.

Although traditional optimization methods focus on finding a single optimal solution, most objective functions in modern machine learning problems, especially those in deep learning, often have multiple or infinite number of optimal points. Therefore, it is useful to consider the problem of finding a set of diverse points in the optimum set of an objective function. In this work, we frame this problem as a bi-level optimization problem of maximizing a diversity score inside the optimum set of the main loss function, and solve it with a simple population gradient descent framework that iteratively updates the points to maximize the diversity score in a fashion that does not hurt the optimization of the main loss. We demonstrate that our method can efficiently generate diverse solutions on multiple applications, e.g. text-to-image generation, text-to-mesh generation, molecular conformation generation and ensemble neural network training.

Natural language understanding and generation models follow one of the two dominant architectural paradigms: language models (LMs) that process concatenated sequences in a single stack of layers, and encoder-decoder models (EncDec) that utilize separate layer stacks for input and output processing. In machine translation, EncDec has long been the favoured approach, but with few studies investigating the performance of LMs. In this work, we thoroughly examine the role of several architectural design choices on the performance of LMs on bilingual, (massively) multilingual and zero-shot translation tasks, under systematic variations of data conditions and model sizes. Our results show that: (i) Different LMs have different scaling properties, where architectural differences often have a significant impact on model performance at small scales, but the performance gap narrows as the number of parameters increases, (ii) Several design choices, including causal masking and language-modeling objectives for the source sequence, have detrimental effects on translation quality, and (iii) When paired with full-visible masking for source sequences, LMs could perform on par with EncDec on supervised bilingual and multilingual translation tasks, and improve greatly on zero-shot directions by facilitating the reduction of off-target translations.

Spiking Neural Networks (SNNs) are considered a promising alternative to Artificial Neural Networks (ANNs) for their event-driven computing paradigm when deployed on energy-efficient neuromorphic hardware. Recently, deep SNNs have shown breathtaking performance improvement through cutting-edge training strategy and flexible structure, which also scales up the number of parameters and computational burdens in a single network. Inspired by the state transition of dendritic spines in the filopodial model of spinogenesis, we model different states of SNN weights, facilitating weight optimization for pruning. Furthermore, the pruning speed can be regulated by using different functions describing the growing threshold of state transition. We organize these techniques as a dynamic pruning algorithm based on nonlinear reparameterization mapping from spine size to SNN weights. Our approach yields sparse deep networks on the large-scale dataset (SEW ResNet18 on ImageNet) while maintaining state-of-the-art low performance loss (~3% at 88.8% sparsity) compared to existing pruning methods on directly trained SNNs. Moreover, we find out pruning speed regulation while learning is crucial to avoiding disastrous performance degradation at the final stages of training, which may shed light on future work on SNN pruning.