Large-scale sequence modeling has sparked rapid advances that now extend into biology and genomics. However, modeling genomic sequences introduces challenges such as the need to model long-range token interactions, the effects of upstream and downstream regions of the genome, and the reverse complementarity (RC) of DNA. Here, we propose an architecture motivated by these challenges that builds off the long-range Mamba block, and extends it to a BiMamba component that supports bi-directionality, and to a MambaDNA block that additionally supports RC equivariance. We use MambaDNA as the basis of Caduceus, the first family of RC equivariant bi-directional long-range DNA language models, and we introduce pre-training and fine-tuning strategies that yield Caduceus DNA foundation models. Caduceus outperforms previous long-range models on downstream benchmarks; on a challenging long-range variant effect prediction task, Caduceus exceeds the performance of 10x larger models that do not leverage bi-directionality or equivariance. Code to reproduce our experiments is available here: https://github.com/kuleshov-group/caduceus.

Despite its widespread use in neural networks, error backpropagation has faced criticism for its lack of biological plausibility, suffering from issues such as the backward locking problem and the weight transport problem. These limitations have motivated researchers to explore more biologically plausible learning algorithms that could potentially shed light on how biological neural systems adapt and learn. Inspired by the counter-current exchange mechanisms observed in biological systems, we propose counter-current learning (CCL), a biologically plausible framework for credit assignment in deep learning. This framework employs a feedforward network to process input data and a feedback network to process targets, with each network enhancing the other through anti-parallel signal propagation. By leveraging the more informative signals from the bottom layer of the feedback network to guide the updates of the top layer of the feedforward network and vice versa, CCL enables the simultaneous transformation of source inputs to target outputs and the dynamic mutual influence of these transformations. Experimental results on MNIST, FashionMNIST, CIFAR10, CIFAR100, and STL-10 datasets using multi-layer perceptrons and convolutional neural networks demonstrate that CCL achieves comparable performance to other biological plausible algorithms while offering a more biologically realistic learning mechanism. Furthermore, we showcase the applicability of our approach to an autoencoder task, underscoring its potential for unsupervised representation learning. Our work presents a promising direction for biologically inspired and plausible learning algorithms, offering insights into the mechanisms of learning and adaptation in neural networks.

Clouds in satellite imagery pose a significant challenge for downstream applications.A major challenge in current cloud removal research is the absence of a comprehensive benchmark and a sufficiently large and diverse training dataset.To address this problem, we introduce the largest public dataset -- *AllClear* for cloud removal, featuring 23,742 globally distributed regions of interest (ROIs) with diverse land-use patterns, comprising 4 million images in total. Each ROI includes complete temporal captures from the year 2022, with (1) multi-spectral optical imagery from Sentinel-2 and Landsat 8/9, (2) synthetic aperture radar (SAR) imagery from Sentinel-1, and (3) auxiliary remote sensing products such as cloud masks and land cover maps.We validate the effectiveness of our dataset by benchmarking performance, demonstrating the scaling law - the PSNR rises from $28.47$ to $33.87$ with $30\times$ more data, and conducting ablation studies on the temporal length and the importance of individual modalities. This dataset aims to provide comprehensive coverage of the Earth's surface and promote better cloud removal results.