Opportunities and obstacles for deep learning in biology and medicine.
University of Hawaii at Manoa1, University of Pennsylvania2, University of Michigan3, Harvard University4, GlaxoSmithKline5, Imperial College London6, University of Toronto7, Princess Margaret Cancer Centre8, Vanderbilt University9, Drexel University10, Carnegie Mellon University11, Stanford University12, University of Virginia13, Broad Institute14, Toyota Technological Institute at Chicago15, Trinity University16, Princeton University17, National Institutes of Health18, Howard Hughes Medical Institute19, University of Florida20, University of Colorado Denver21, University of Münster22, Georgetown University Medical Center23, Washington University in St. Louis24, Brown University25, Morgridge Institute for Research26, University of Wisconsin-Madison27
01 Apr 2018-Journal of the Royal Society Interface (The Royal Society)-Vol. 15, Iss: 141, pp 20170387
TL;DR: It is found that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art.
Abstract: Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems-patient classification, fundamental biological processes and treatment of patients-and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine.
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TL;DR: CellProfiler 3.0 is described, a new version of the software supporting both whole-volume and plane-wise analysis of three-dimensional image stacks, increasingly common in biomedical research.
Abstract: CellProfiler has enabled the scientific research community to create flexible, modular image analysis pipelines since its release in 2005. Here, we describe CellProfiler 3.0, a new version of the software supporting both whole-volume and plane-wise analysis of three-dimensional (3D) image stacks, increasingly common in biomedical research. CellProfiler's infrastructure is greatly improved, and we provide a protocol for cloud-based, large-scale image processing. New plugins enable running pretrained deep learning models on images. Designed by and for biologists, CellProfiler equips researchers with powerful computational tools via a well-documented user interface, empowering biologists in all fields to create quantitative, reproducible image analysis workflows.
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TL;DR: Recent breakthroughs in AI technologies and their biomedical applications are outlined, the challenges for further progress in medical AI systems are identified, and the economic, legal and social implications of AI in healthcare are summarized.
Abstract: Artificial intelligence (AI) is gradually changing medical practice. With recent progress in digitized data acquisition, machine learning and computing infrastructure, AI applications are expanding into areas that were previously thought to be only the province of human experts. In this Review Article, we outline recent breakthroughs in AI technologies and their biomedical applications, identify the challenges for further progress in medical AI systems, and summarize the economic, legal and social implications of AI in healthcare.
1,315 citations
TL;DR: In this paper, a comprehensive survey of the most important aspects of DL and including those enhancements recently added to the field is provided, and the challenges and suggested solutions to help researchers understand the existing research gaps.
Abstract: In the last few years, the deep learning (DL) computing paradigm has been deemed the Gold Standard in the machine learning (ML) community. Moreover, it has gradually become the most widely used computational approach in the field of ML, thus achieving outstanding results on several complex cognitive tasks, matching or even beating those provided by human performance. One of the benefits of DL is the ability to learn massive amounts of data. The DL field has grown fast in the last few years and it has been extensively used to successfully address a wide range of traditional applications. More importantly, DL has outperformed well-known ML techniques in many domains, e.g., cybersecurity, natural language processing, bioinformatics, robotics and control, and medical information processing, among many others. Despite it has been contributed several works reviewing the State-of-the-Art on DL, all of them only tackled one aspect of the DL, which leads to an overall lack of knowledge about it. Therefore, in this contribution, we propose using a more holistic approach in order to provide a more suitable starting point from which to develop a full understanding of DL. Specifically, this review attempts to provide a more comprehensive survey of the most important aspects of DL and including those enhancements recently added to the field. In particular, this paper outlines the importance of DL, presents the types of DL techniques and networks. It then presents convolutional neural networks (CNNs) which the most utilized DL network type and describes the development of CNNs architectures together with their main features, e.g., starting with the AlexNet network and closing with the High-Resolution network (HR.Net). Finally, we further present the challenges and suggested solutions to help researchers understand the existing research gaps. It is followed by a list of the major DL applications. Computational tools including FPGA, GPU, and CPU are summarized along with a description of their influence on DL. The paper ends with the evolution matrix, benchmark datasets, and summary and conclusion.
1,084 citations
TL;DR: The first wave of applications of deep learning in pharmaceutical research has emerged in recent years, and its utility has gone beyond bioactivity predictions and has shown promise in addressing diverse problems in drug discovery.
1,068 citations
TL;DR: This work shows that recurrent neural networks can be trained as generative models for molecular structures, similar to statistical language models in natural language processing, and demonstrates that the properties of the generated molecules correlate very well with those of the molecules used to train the model.
Abstract: In de novo drug design, computational strategies are used to generate novel molecules with good affinity to the desired biological target. In this work, we show that recurrent neural networks can be trained as generative models for molecular structures, similar to statistical language models in natural language processing. We demonstrate that the properties of the generated molecules correlate very well with the properties of the molecules used to train the model. In order to enrich libraries with molecules active toward a given biological target, we propose to fine-tune the model with small sets of molecules, which are known to be active against that target. Against Staphylococcus aureus, the model reproduced 14% of 6051 hold-out test molecules that medicinal chemists designed, whereas against Plasmodium falciparum (Malaria), it reproduced 28% of 1240 test molecules. When coupled with a scoring function, our model can perform the complete de novo drug design cycle to generate large sets of novel molecule...
1,041 citations
References
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27 Jun 2016
TL;DR: In this article, the authors proposed a residual learning framework to ease the training of networks that are substantially deeper than those used previously, which won the 1st place on the ILSVRC 2015 classification task.
Abstract: Deeper neural networks are more difficult to train. We present a residual learning framework to ease the training of networks that are substantially deeper than those used previously. We explicitly reformulate the layers as learning residual functions with reference to the layer inputs, instead of learning unreferenced functions. We provide comprehensive empirical evidence showing that these residual networks are easier to optimize, and can gain accuracy from considerably increased depth. On the ImageNet dataset we evaluate residual nets with a depth of up to 152 layers—8× deeper than VGG nets [40] but still having lower complexity. An ensemble of these residual nets achieves 3.57% error on the ImageNet test set. This result won the 1st place on the ILSVRC 2015 classification task. We also present analysis on CIFAR-10 with 100 and 1000 layers. The depth of representations is of central importance for many visual recognition tasks. Solely due to our extremely deep representations, we obtain a 28% relative improvement on the COCO object detection dataset. Deep residual nets are foundations of our submissions to ILSVRC & COCO 2015 competitions1, where we also won the 1st places on the tasks of ImageNet detection, ImageNet localization, COCO detection, and COCO segmentation.
123,388 citations
Proceedings Article•
03 Dec 2012TL;DR: The state-of-the-art performance of CNNs was achieved by Deep Convolutional Neural Networks (DCNNs) as discussed by the authors, which consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully-connected layers with a final 1000-way softmax.
Abstract: We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 different classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0% which is considerably better than the previous state-of-the-art. The neural network, which has 60 million parameters and 650,000 neurons, consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully-connected layers with a final 1000-way softmax. To make training faster, we used non-saturating neurons and a very efficient GPU implementation of the convolution operation. To reduce overriding in the fully-connected layers we employed a recently-developed regularization method called "dropout" that proved to be very effective. We also entered a variant of this model in the ILSVRC-2012 competition and achieved a winning top-5 test error rate of 15.3%, compared to 26.2% achieved by the second-best entry.
73,978 citations
TL;DR: In this article, the product-limit (PL) estimator was proposed to estimate the proportion of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t).
Abstract: In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed. For random samples of size N the product-limit (PL) estimate can be defined as follows: L...
52,450 citations
"Opportunities and obstacles for dee..." refers background in this paper
...This results in loss of information as timing and order of events can provide insight into a patient's disease and treatment [135]....
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05 Oct 2015
TL;DR: Neber et al. as discussed by the authors proposed a network and training strategy that relies on the strong use of data augmentation to use the available annotated samples more efficiently, which can be trained end-to-end from very few images and outperforms the prior best method (a sliding-window convolutional network) on the ISBI challenge for segmentation of neuronal structures in electron microscopic stacks.
Abstract: There is large consent that successful training of deep networks requires many thousand annotated training samples. In this paper, we present a network and training strategy that relies on the strong use of data augmentation to use the available annotated samples more efficiently. The architecture consists of a contracting path to capture context and a symmetric expanding path that enables precise localization. We show that such a network can be trained end-to-end from very few images and outperforms the prior best method (a sliding-window convolutional network) on the ISBI challenge for segmentation of neuronal structures in electron microscopic stacks. Using the same network trained on transmitted light microscopy images (phase contrast and DIC) we won the ISBI cell tracking challenge 2015 in these categories by a large margin. Moreover, the network is fast. Segmentation of a 512x512 image takes less than a second on a recent GPU. The full implementation (based on Caffe) and the trained networks are available at http://lmb.informatik.uni-freiburg.de/people/ronneber/u-net .
49,590 citations
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TL;DR: Deep learning is making major advances in solving problems that have resisted the best attempts of the artificial intelligence community for many years, and will have many more successes in the near future because it requires very little engineering by hand and can easily take advantage of increases in the amount of available computation and data.
Abstract: Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
46,982 citations