Christopher S. Poultney

Bio: Christopher S. Poultney is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Regulation of gene expression & Exome. The author has an hindex of 15, co-authored 18 publications receiving 5866 citations. Previous affiliations of Christopher S. Poultney include Courant Institute of Mathematical Sciences & New York University.

Synaptic, transcriptional and chromatin genes disrupted in autism

Abstract: The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

Wisdom of crowds for robust gene network inference

Abstract: Reconstructing gene regulatory networks from high-throughput data is a long-standing challenge. Through the Dialogue on Reverse Engineering Assessment and Methods (DREAM) project, we performed a comprehensive blind assessment of over 30 network inference methods on Escherichia coli, Staphylococcus aureus, Saccharomyces cerevisiae and in silico microarray data. We characterize the performance, data requirements and inherent biases of different inference approaches, and we provide guidelines for algorithm application and development. We observed that no single inference method performs optimally across all data sets. In contrast, integration of predictions from multiple inference methods shows robust and high performance across diverse data sets. We thereby constructed high-confidence networks for E. coli and S. aureus, each comprising ∼1,700 transcriptional interactions at a precision of ∼50%. We experimentally tested 53 previously unobserved regulatory interactions in E. coli, of which 23 (43%) were supported. Our results establish community-based methods as a powerful and robust tool for the inference of transcriptional gene regulatory networks.

Efficient Learning of Sparse Representations with an Energy-Based Model

Abstract: We describe a novel unsupervised method for learning sparse, overcomplete features. The model uses a linear encoder, and a linear decoder preceded by a sparsifying non-linearity that turns a code vector into a quasi-binary sparse code vector. Given an input, the optimal code minimizes the distance between the output of the decoder and the input patch while being as similar as possible to the encoder output. Learning proceeds in a two-phase EM-like fashion: (1) compute the minimum-energy code vector, (2) adjust the parameters of the encoder and decoder so as to decrease the energy. The model produces "stroke detectors" when trained on handwritten numerals, and Gabor-like filters when trained on natural image patches. Inference and learning are very fast, requiring no preprocessing, and no expensive sampling. Using the proposed unsupervised method to initialize the first layer of a convolutional network, we achieved an error rate slightly lower than the best reported result on the MNIST dataset. Finally, an extension of the method is described to learn topographical filter maps.

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Abstract: We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.

Deep Learning

Abstract: Deep learning is a form of machine learning that enables computers to learn from experience and understand the world in terms of a hierarchy of concepts. Because the computer gathers knowledge from experience, there is no need for a human computer operator to formally specify all the knowledge that the computer needs. The hierarchy of concepts allows the computer to learn complicated concepts by building them out of simpler ones; a graph of these hierarchies would be many layers deep. This book introduces a broad range of topics in deep learning. The text offers mathematical and conceptual background, covering relevant concepts in linear algebra, probability theory and information theory, numerical computation, and machine learning. It describes deep learning techniques used by practitioners in industry, including deep feedforward networks, regularization, optimization algorithms, convolutional networks, sequence modeling, and practical methodology; and it surveys such applications as natural language processing, speech recognition, computer vision, online recommendation systems, bioinformatics, and videogames. Finally, the book offers research perspectives, covering such theoretical topics as linear factor models, autoencoders, representation learning, structured probabilistic models, Monte Carlo methods, the partition function, approximate inference, and deep generative models. Deep Learning can be used by undergraduate or graduate students planning careers in either industry or research, and by software engineers who want to begin using deep learning in their products or platforms. A website offers supplementary material for both readers and instructors.

Representation Learning: A Review and New Perspectives

Abstract: The success of machine learning algorithms generally depends on data representation, and we hypothesize that this is because different representations can entangle and hide more or less the different explanatory factors of variation behind the data. Although specific domain knowledge can be used to help design representations, learning with generic priors can also be used, and the quest for AI is motivating the design of more powerful representation-learning algorithms implementing such priors. This paper reviews recent work in the area of unsupervised feature learning and deep learning, covering advances in probabilistic models, autoencoders, manifold learning, and deep networks. This motivates longer term unanswered questions about the appropriate objectives for learning good representations, for computing representations (i.e., inference), and the geometrical connections between representation learning, density estimation, and manifold learning.

Understanding the difficulty of training deep feedforward neural networks

Abstract: Whereas before 2006 it appears that deep multilayer neural networks were not successfully trained, since then several algorithms have been shown to successfully train them, with experimental results showing the superiority of deeper vs less deep architectures. All these experimental results were obtained with new initialization or training mechanisms. Our objective here is to understand better why standard gradient descent from random initialization is doing so poorly with deep neural networks, to better understand these recent relative successes and help design better algorithms in the future. We first observe the influence of the non-linear activations functions. We find that the logistic sigmoid activation is unsuited for deep networks with random initialization because of its mean value, which can drive especially the top hidden layer into saturation. Surprisingly, we find that saturated units can move out of saturation by themselves, albeit slowly, and explaining the plateaus sometimes seen when training neural networks. We find that a new non-linearity that saturates less can often be beneficial. Finally, we study how activations and gradients vary across layers and during training, with the idea that training may be more difficult when the singular values of the Jacobian associated with each layer are far from 1. Based on these considerations, we propose a new initialization scheme that brings substantially faster convergence. 1 Deep Neural Networks Deep learning methods aim at learning feature hierarchies with features from higher levels of the hierarchy formed by the composition of lower level features. They include Appearing in Proceedings of the 13 International Conference on Artificial Intelligence and Statistics (AISTATS) 2010, Chia Laguna Resort, Sardinia, Italy. Volume 9 of JMLR: WC Weston et al., 2008). Much attention has recently been devoted to them (see (Bengio, 2009) for a review), because of their theoretical appeal, inspiration from biology and human cognition, and because of empirical success in vision (Ranzato et al., 2007; Larochelle et al., 2007; Vincent et al., 2008) and natural language processing (NLP) (Collobert & Weston, 2008; Mnih & Hinton, 2009). Theoretical results reviewed and discussed by Bengio (2009), suggest that in order to learn the kind of complicated functions that can represent high-level abstractions (e.g. in vision, language, and other AI-level tasks), one may need deep architectures. Most of the recent experimental results with deep architecture are obtained with models that can be turned into deep supervised neural networks, but with initialization or training schemes different from the classical feedforward neural networks (Rumelhart et al., 1986). Why are these new algorithms working so much better than the standard random initialization and gradient-based optimization of a supervised training criterion? Part of the answer may be found in recent analyses of the effect of unsupervised pretraining (Erhan et al., 2009), showing that it acts as a regularizer that initializes the parameters in a “better” basin of attraction of the optimization procedure, corresponding to an apparent local minimum associated with better generalization. But earlier work (Bengio et al., 2007) had shown that even a purely supervised but greedy layer-wise procedure would give better results. So here instead of focusing on what unsupervised pre-training or semi-supervised criteria bring to deep architectures, we focus on analyzing what may be going wrong with good old (but deep) multilayer neural networks. Our analysis is driven by investigative experiments to monitor activations (watching for saturation of hidden units) and gradients, across layers and across training iterations. We also evaluate the effects on these of choices of activation function (with the idea that it might affect saturation) and initialization procedure (since unsupervised pretraining is a particular form of initialization and it has a drastic impact).

Machine Learning : A Probabilistic Perspective

Abstract: Today's Web-enabled deluge of electronic data calls for automated methods of data analysis. Machine learning provides these, developing methods that can automatically detect patterns in data and then use the uncovered patterns to predict future data. This textbook offers a comprehensive and self-contained introduction to the field of machine learning, based on a unified, probabilistic approach. The coverage combines breadth and depth, offering necessary background material on such topics as probability, optimization, and linear algebra as well as discussion of recent developments in the field, including conditional random fields, L1 regularization, and deep learning. The book is written in an informal, accessible style, complete with pseudo-code for the most important algorithms. All topics are copiously illustrated with color images and worked examples drawn from such application domains as biology, text processing, computer vision, and robotics. Rather than providing a cookbook of different heuristic methods, the book stresses a principled model-based approach, often using the language of graphical models to specify models in a concise and intuitive way. Almost all the models described have been implemented in a MATLAB software package--PMTK (probabilistic modeling toolkit)--that is freely available online. The book is suitable for upper-level undergraduates with an introductory-level college math background and beginning graduate students.