RECOVER identifies synergistic drug combinations in vitro through sequential model optimization.

For large libraries of small molecules, exhaustive combinatorial chemical screens become infeasible to perform when considering a range of disease models, assay conditions, and dose ranges. Deep learning models have achieved state-of-the-art results in silico for the prediction of synergy scores. However, databases of drug combinations are biased toward synergistic agents and results do not generalize out of distribution. During 5 rounds of experimentation, we employ sequential model optimization with a deep learning model to select drug combinations increasingly enriched for synergism and active against a cancer cell line-evaluating only ∼5% of the total search space. Moreover, we find that learned drug embeddings (using structural information) begin to reflect biological mechanisms. In silico benchmarking suggests search queries are ∼5-10× enriched for highly synergistic drug combinations by using sequential rounds of evaluation when compared with random selection or ∼3× when using a pretrained model.

Graph-in-Graph (GiG): Learning interpretable latent graphs in non-Euclidean domain for biological and healthcare applications.

Graphs are a powerful tool for representing and analyzing unstructured, non-Euclidean data ubiquitous in the healthcare domain. Two prominent examples are molecule property prediction and brain connectome analysis. Importantly, recent works have shown that considering relationships between input data samples has a positive regularizing effect on the downstream task in healthcare applications. These relationships are naturally modeled by a (possibly unknown) graph structure between input samples. In this work, we propose Graph-in-Graph (GiG), a neural network architecture for protein classification and brain imaging applications that exploits the graph representation of the input data samples and their latent relation. We assume an initially unknown latent-graph structure between graph-valued input data and propose to learn a parametric model for message passing within and across input graph samples, end-to-end along with the latent structure connecting the input graphs. Further, we introduce a Node Degree Distribution Loss (NDDL) that regularizes the predicted latent relationships structure. This regularization can significantly improve the downstream task. Moreover, the obtained latent graph can represent patient population models or networks of molecule clusters, providing a level of interpretability and knowledge discovery in the input domain, which is of particular value in healthcare.

Improving Graph Neural Network Expressivity via Subgraph Isomorphism Counting.

While Graph Neural Networks (GNNs) have achieved remarkable results in a variety of applications, recent studies exposed important shortcomings in their ability to capture the structure of the underlying graph. It has been shown that the expressive power of standard GNNs is bounded by the Weisfeiler-Leman (WL) graph isomorphism test, from which they inherit proven limitations such as the inability to detect and count graph substructures. On the other hand, there is significant empirical evidence, e.g. in network science and bioinformatics, that substructures are often intimately related to downstream tasks. To this end, we propose "Graph Substructure Networks" (GSN), a topologically-aware message passing scheme based on substructure encoding. We theoretically analyse the expressive power of our architecture, showing that it is strictly more expressive than the WL test, and provide sufficient conditions for universality. Importantly, we do not attempt to adhere to the WL hierarchy; this allows us to retain multiple attractive properties of standard GNNs such as locality and linear network complexity, while being able to disambiguate even hard instances of graph isomorphism. We perform an extensive experimental evaluation on graph classification and regression tasks and obtain state-of-the-art results in diverse real-world settings including molecular graphs and social networks.

Differentiable Graph Module (DGM) for Graph Convolutional Networks.

Graph deep learning has recently emerged as a powerful ML concept allowing to generalize successful deep neural architectures to non-euclidean structured data. Such methods have shown promising results on a broad spectrum of applications ranging from social science, biomedicine, and particle physics to computer vision, graphics, and chemistry. One of the limitations of the majority of current graph neural network architectures is that they are often restricted to the transductive setting and rely on the assumption that the underlying graph is known and fixed. Often, this assumption is not true since the graph may be noisy, or partially and even completely unknown. In such cases, it would be helpful to infer the graph directly from the data, especially in inductive settings where some nodes were not present in the graph at training time. Furthermore, learning a graph may become an end in itself, as the inferred structure may provide complementary insights next to the downstream task. In this paper, we introduce Differentiable Graph Module (DGM), a learnable function that predicts edge probabilities in the graph which are optimal for the downstream task. DGM can be combined with convolutional graph neural network layers and trained in an end-to-end fashion. We provide an extensive evaluation of applications from the domains of healthcare (disease prediction), brain imaging (age prediction), computer graphics (3D point cloud segmentation), and computer vision (zero-shot learning). We show that our model provides a significant improvement over baselines both in transductive and inductive settings and achieves state-of-the-art results.

Toward understanding the communication in sperm whales.

Machine learning has been advancing dramatically over the past decade. Most strides are human-based applications due to the availability of large-scale datasets; however, opportunities are ripe to apply this technology to more deeply understand non-human communication. We detail a scientific roadmap for advancing the understanding of communication of whales that can be built further upon as a template to decipher other forms of animal and non-human communication. Sperm whales, with their highly developed neuroanatomical features, cognitive abilities, social structures, and discrete click-based encoding make for an excellent model for advanced tools that can be applied to other animals in the future. We outline the key elements required for the collection and processing of massive datasets, detecting basic communication units and language-like higher-level structures, and validating models through interactive playback experiments. The technological capabilities developed by such an undertaking hold potential for cross-applications in broader communities investigating non-human communication and behavioral research.

Utilizing graph machine learning within drug discovery and development.

Graph machine learning (GML) is receiving growing interest within the pharmaceutical and biotechnology industries for its ability to model biomolecular structures, the functional relationships between them, and integrate multi-omic datasets - amongst other data types. Herein, we present a multidisciplinary academic-industrial review of the topic within the context of drug discovery and development. After introducing key terms and modelling approaches, we move chronologically through the drug development pipeline to identify and summarize work incorporating: target identification, design of small molecules and biologics, and drug repurposing. Whilst the field is still emerging, key milestones including repurposed drugs entering in vivo studies, suggest GML will become a modelling framework of choice within biomedical machine learning.

Intel® RealSense™ SR300 Coded Light Depth Camera.

Intel® RealSense™ SR300 is a depth camera capable of providing a VGA-size depth map at 60 fps and 0.125mm depth resolution. In addition, it outputs an infrared VGA-resolution image and a 1080p color texture image at 30 fps. SR300 form-factor enables it to be integrated into small consumer products and as a front facing camera in laptops and Ultrabooks™. The SR300 depth camera is based on a coded-light technology where triangulation between projected patterns and images captured by a dedicated sensor is used to produce the depth map. Each projected line is coded by a special temporal optical code, that enables a dense depth map reconstruction from its reflection. The solid mechanical assembly of the camera allows it to stay calibrated throughout temperature and pressure changes, drops, and hits. In addition, active dynamic control maintains a calibrated depth output. An extended API LibRS released with the camera allows developers to integrate the camera in various applications. Algorithms for 3D scanning, facial analysis, hand gesture recognition, and tracking are within reach for applications using the SR300. In this paper, we describe the underlying technology, hardware, and algorithms of the SR300, as well as its calibration procedure, and outline some use cases. We believe that this paper will provide a full case study of a mass-produced depth sensing product and technology.

Publisher Correction: Deep Machine Learning Techniques for the Detection and Classification of Sperm Whale Bioacoustics.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Deep Machine Learning Techniques for the Detection and Classification of Sperm Whale Bioacoustics.

We implemented Machine Learning (ML) techniques to advance the study of sperm whale (Physeter macrocephalus) bioacoustics. This entailed employing Convolutional Neural Networks (CNNs) to construct an echolocation click detector designed to classify spectrograms generated from sperm whale acoustic data according to the presence or absence of a click. The click detector achieved 99.5% accuracy in classifying 650 spectrograms. The successful application of CNNs to clicks reveals the potential of future studies to train CNN-based architectures to extract finer-scale details from cetacean spectrograms. Long short-term memory and gated recurrent unit recurrent neural networks were trained to perform classification tasks, including (1) "coda type classification" where we obtained 97.5% accuracy in categorizing 23 coda types from a Dominica dataset containing 8,719 codas and 93.6% accuracy in categorizing 43 coda types from an Eastern Tropical Pacific (ETP) dataset with 16,995 codas; (2) "vocal clan classification" where we obtained 95.3% accuracy for two clan classes from Dominica and 93.1% for four ETP clan types; and (3) "individual whale identification" where we obtained 99.4% accuracy using two Dominica sperm whales. These results demonstrate the feasibility of applying ML to sperm whale bioacoustics and establish the validity of constructing neural networks to learn meaningful representations of whale vocalizations.

Multimodal Manifold Analysis by Simultaneous Diagonalization of Laplacians.

We construct an extension of spectral and diffusion geometry to multiple modalities through simultaneous diagonalization of Laplacian matrices. This naturally extends classical data analysis tools based on spectral geometry, such as diffusion maps and spectral clustering. We provide several synthetic and real examples of manifold learning, object classification, and clustering, showing that the joint spectral geometry better captures the inherent structure of multi-modal data. We also show the relation of many previous approaches for multimodal manifold analysis to our framework.

Multimodal Similarity-Preserving Hashing.

We introduce an efficient computational framework for hashing data belonging to multiple modalities into a single representation space where they become mutually comparable. The proposed approach is based on a novel coupled siamese neural network architecture and allows unified treatment of intra- and inter-modality similarity learning. Unlike existing cross-modality similarity learning approaches, our hashing functions are not limited to binarized linear projections and can assume arbitrarily complex forms. We show experimentally that our method significantly outperforms state-of-the-art hashing approaches on multimedia retrieval tasks.

Are MSER features really interesting?

Detection and description of affine-invariant features is a cornerstone component in numerous computer vision applications. In this note, we analyze the notion of maximally stable extremal regions (MSERs) through the prism of the curvature scale space, and conclude that in its original definition, MSER prefers regular (round) regions. Arguing that interesting features in natural images usually have irregular shapes, we propose alternative definitions of MSER which are free of this bias, yet maintain their invariance properties.

Shape recognition with spectral distances.

Recent works have shown the use of diffusion geometry for various pattern recognition applications, including nonrigid shape analysis. In this paper, we introduce spectral shape distance as a general framework for distribution-based shape similarity and show that two recent methods for shape similarity due to Rustamov and Mahmoudi and Sapiro are particular cases thereof.

Lazy sliding window implementation of the bilateral filter on parallel architectures.

Bilateral filter is one of the state-of-the-art methods for noise reduction in images. The plausible visual result the filter produces makes it a common choice for image and video processing applications, yet, its high computational complexity makes a real-time implementation a challenging task. Presented here is a parallel version of the bilateral filter using a lazy sliding window, suitable for SIMD-type architectures.

Expression-invariant representations of faces.

Addressed here is the problem of constructing and analyzing expression-invariant representations of human faces. We demonstrate and justify experimentally a simple geometric model that allows to describe facial expressions as isometric deformations of the facial surface. The main step in the construction of expression-invariant representation of a face involves embedding of the facial intrinsic geometric structure into some low-dimensional space. We study the influence of the embedding space geometry and dimensionality choice on the representation accuracy and argue that compared to its Euclidean counterpart, spherical embedding leads to notably smaller metric distortions. We experimentally support our claim showing that a smaller embedding error leads to better recognition.

Generalized multidimensional scaling: a framework for isometry-invariant partial surface matching.

An efficient algorithm for isometry-invariant matching of surfaces is presented. The key idea is computing the minimum-distortion mapping between two surfaces. For this purpose, we introduce the generalized multidimensional scaling, a computationally efficient continuous optimization algorithm for finding the least distortion embedding of one surface into another. The generalized multidimensional scaling algorithm allows for both full and partial surface matching. As an example, it is applied to the problem of expression-invariant three-dimensional face recognition.

Blind deconvolution of images using optimal sparse representations.

The relative Newton algorithm, previously proposed for quasi-maximum likelihood blind source separation and blind deconvolution of one-dimensional signals is generalized for blind deconvolution of images. Smooth approximation of the absolute value is used as the nonlinear term for sparse sources. In addition, we propose a method of sparsification, which allows blind deconvolution of arbitrary sources, and show how to find optimal sparsifying transformations by supervised learning.

Reconstruction in diffraction ultrasound tomography using nonuniform FFT.

We show an iterative reconstruction framework for diffraction ultrasound tomography. The use of broad-band illumination allows significant reduction of the number of projections compared to straight ray tomography. The proposed algorithm makes use of forward nonuniform fast Fourier transform (NUFFT) for iterative Fourier inversion. Incorporation of total variation regularization allows the reduction of noise and Gibbs phenomena while preserving the edges. The complexity of the NUFFT-based reconstruction is comparable to the frequency-domain interpolation (gridding) algorithm, whereas the reconstruction accuracy (in sense of the L2 and the L(infinity) norm) is better.