sincFold: end-to-end learning of short- and long-range interactions in RNA secondary structure.

MOTIVATION: Coding and noncoding RNA molecules participate in many important biological processes. Noncoding RNAs fold into well-defined secondary structures to exert their functions. However, the computational prediction of the secondary structure from a raw RNA sequence is a long-standing unsolved problem, which after decades of almost unchanged performance has now re-emerged due to deep learning. Traditional RNA secondary structure prediction algorithms have been mostly based on thermodynamic models and dynamic programming for free energy minimization. More recently deep learning methods have shown competitive performance compared with the classical ones, but there is still a wide margin for improvement. RESULTS: In this work we present sincFold, an end-to-end deep learning approach, that predicts the nucleotides contact matrix using only the RNA sequence as input. The model is based on 1D and 2D residual neural networks that can learn short- and long-range interaction patterns. We show that structures can be accurately predicted with minimal physical assumptions. Extensive experiments were conducted on several benchmark datasets, considering sequence homology and cross-family validation. sincFold was compared with classical methods and recent deep learning models, showing that it can outperform the state-of-the-art methods.

Boundary-aware glomerulus segmentation: Toward one-to-many stain generalization.

The growing availability of scanned whole-slide images (WSIs) has allowed nephropathology to open new possibilities for medical decision-making over high-resolution images. Diagnosis of renal WSIs includes locating and identifying specific structures in the tissue. Considering the glomerulus as one of the first structures analyzed by pathologists, we propose here a novel convolutional neural network for glomerulus segmentation. Our end-to-end network, named DS-FNet, combines the strengths of semantic segmentation and semantic boundary detection networks via an attention-aware mechanism. Although we trained the proposed network on periodic acid-Schiff (PAS)-stained WSIs, we found that our network was capable to segment glomeruli on WSIs stained with different techniques, such as periodic acid-methenamine silver (PAMS), hematoxylin-eosin (HE), and Masson trichrome (TRI). To assess the performance of the proposed method, we used three public data sets: HuBMAP (available in a Kaggle competition), a subset of the NEPTUNE data set, and a novel challenging data set, called WSI_Fiocruz. We compared the DS-FNet with six other deep learning networks: original U-Net, our attention version of U-Net called AU-Net, U-Net++, U-Net3Plus, ResU-Net, and DeepLabV3+. Results showed that DS-FNet achieved equivalent or superior results on all data sets: On the HuBMAP data set, it reached a dice score (DSC) of 95.05%, very close to the first place (95.15%); on the NEPTUNE and WSI_Fiocruz data sets, DS-FNet obtained the highest average DSC, whether on PAS-stained images or images stained with other techniques. To the best we know, this is the first work to show consistently high performance in a one-to-many-stain glomerulus segmentation following a thorough protocol on data sets from different medical labs.