Sleep stage classification constitutes an important preliminary exam in the diagnosis of sleep disorders. It is traditionally performed by a sleep expert who assigns to each 30 s of the signal of a sleep stage, based on the visual inspection of signals such as electroencephalograms (EEGs), electrooculograms (EOGs), electrocardiograms, and electromyograms (EMGs). We introduce here the first deep learning approach for sleep stage classification that learns end-to-end without computing spectrograms or extracting handcrafted features, that exploits all multivariate and multimodal polysomnography (PSG) signals (EEG, EMG, and EOG), and that can exploit the temporal context of each 30-s window of data. For each modality, the first layer learns linear spatial filters that exploit the array of sensors to increase the signal-to-noise ratio, and the last layer feeds the learnt representation to a softmax classifier. Our model is compared to alternative automatic approaches based on convolutional networks or decisions trees. Results obtained on 61 publicly available PSG records with up to 20 EEG channels demonstrate that our network architecture yields the state-of-the-art performance. Our study reveals a number of insights on the spatiotemporal distribution of the signal of interest: a good tradeoff for optimal classification performance measured with balanced accuracy is to use 6 EEG with 2 EOG (left and right) and 3 EMG chin channels. Also exploiting 1 min of data before and after each data segment offers the strongest improvement when a limited number of channels are available. As sleep experts, our system exploits the multivariate and multimodal nature of PSG signals in order to deliver the state-of-the-art classification performance with a small computational cost.

Deep learning methods for digital pathology analysis are an effective way to address multiple clinical questions, from diagnosis to prediction of treatment outcomes. These methods have also been used to predict gene mutations from pathology images, but no comprehensive evaluation of their potential for extracting molecular features from histology slides has yet been performed. We show that HE2RNA, a model based on the integration of multiple data modes, can be trained to systematically predict RNA-Seq profiles from whole-slide images alone, without expert annotation. Through its interpretable design, HE2RNA provides virtual spatialization of gene expression, as validated by CD3-and CD20-staining on an independent dataset. The transcriptomic representation learned by HE2RNA can also be transferred on other datasets, even of small size, to increase prediction performance for specific molecular phenotypes. We illustrate the use of this approach in clinical diagnosis purposes such as the identification of tumors with microsatellite instability.

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BaCKgRoUND aND aIMS: Standardized and robust risk-stratification systems for patients with hepatocellular carcinoma (HCC) are required to improve therapeutic strategies and investigate the benefits of adjuvant systemic therapies after curative resection/ablation. appRoaCH aND ReSUltS: In this study, we used two deep-learning algorithms based on whole-slide digitized histological slides (whole-slide imaging; WSI) to build models for predicting survival of patients with HCC treated by surgical resection. Two independent series were investigated: a discovery set (Henri Mondor Hospital, n = 194) used to develop our algorithms and an independent validation set (The Cancer Genome Atlas [TCGA], n = 328). WSIs were first divided into small squares ("tiles"), and features were extracted with a pretrained convolutional neural network (preprocessing step). The first deep-learning-based algorithm ("SCHMOWDER") uses an attention mechanism on tumoral areas annotated by a pathologist whereas the second ("CHOWDER") does not require human expertise. In the discovery set, c-indices for survival prediction of SCHMOWDER and CHOWDER reached 0.78 and 0.75, respectively. Both models outperformed a composite score incorporating all baseline variables associated with survival. Prognostic value of the models was further validated in the TCGA data set, and, as observed in the discovery series, both models had a higher discriminatory power than a score combining all baseline variables associated with survival. Pathological review showed that the tumoral areas most predictive of poor survival were characterized by vascular spaces, the macrotrabecular architectural pattern, and a lack of immune infiltration. CoNClUSIoNS: This study shows that artificial intelligence can help refine the prediction of HCC prognosis. It highlights the importance of pathologist/machine interactions for the construction of deep-learning algorithms that benefit from expert knowledge and allow a biological understanding of their output.

Random neural networks are dynamical descriptions of randomly interconnected neural units. These show a phase transition to chaos as a disorder parameter is increased. The microscopic mechanisms underlying this phase transition are unknown, and similarly to spin-glasses, shall be fundamentally related to the behavior of the system. In this Letter we investigate the explosion of complexity arising near that phase transition. We show that the mean number of equilibria undergoes a sharp transition from one equilibrium to a very large number scaling exponentially with the dimension on the system. Near criticality, we compute the exponential rate of divergence, called topological complexity. Strikingly, we show that it behaves exactly as the maximal Lyapunov exponent, a classical measure of dynamical complexity. This relationship unravels a microscopic mechanism leading to chaos which we further demonstrate on a simpler disordered systems, suggesting a deep and underexplored link between topological and dynamical complexity. Heterogeneity of interconnections is a crucial property to understand the behavior of realistic networks that arise in the modeling of physical, biological or social complex systems. Among these, a paramount example is given by neuronal networks of the brain. In these systems, synaptic connections display characteristic disorder properties [1,2] resulting from development and learning. Taking into account this heterogeneity seems now essential, as experimental studies of neuronal tissues have shown that the degree of disorder in the connections significantly impacts the input-output function, rhythmicity and synchrony, effects that can be related to transitions between physiological and pathological behaviors [3][4][5]. As an example, Aradi and Soltesz [3] have shown that rats subject to febrile seizure present the same average synaptic properties but increased variance.These properties are reminiscent of disordered physical systems such as spin-glasses. The relationship between disorder and qualitative behaviors has been thoroughly studied within theoretical frameworks such as the Sherrington-Kirkpatrick model [6] describing the behavior of binary variables interacting through a random connectivity matrix. In these models, estimating the number of metastable states, deemed to be deeply related to the transition to chaos, remains an important endeavor [7]. In the context of nervous system modeling, random neural networks [8,9] constitute a prominent class of models, which describe the evolution of the activity of a neuron i in a n-neurons network through the randomly coupled system of ordinary differential equations:where J ij are independent centered Gaussian random variables of variance σ 2 /n representing the synaptic connectivity coefficients between neuron i and j [10], and S is an odd sigmoid function with maximal unit slope at the origin (S (x) ≤ S (0) = 1) representing the synaptic nonlinearity.The behavior of system (1) has been analyzed in the asymptotic regime of infinite population si...