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Chris Wiggins

Publications and source records attributed to Chris Wiggins.

11 recordsLinked to original sources
arXiv2020

An Agenda for Disinformation Research

In the 21st Century information environment, adversarial actors use disinformation to manipulate public opinion. The distribution of false, misleading, or inaccurate information with the intent to deceive is an existential threat to the United States--distortion of information erodes trust in the socio-political institutions that are the fundamental fabric of democracy: legitimate news sources, scientists, experts, and even fellow citizens. As a result, it becomes difficult for society to come together within a shared reality; the common ground needed to function effectively as an economy and a nation. Computing and communication technologies have facilitated the exchange of information at unprecedented speeds and scales. This has had countless benefits to society and the economy, but it has also played a fundamental role in the rising volume, variety, and velocity of disinformation. Technological advances have created new opportunities for manipulation, influence, and deceit. They have effectively lowered the barriers to reaching large audiences, diminishing the role of traditional mass media along with the editorial oversight they provided. The digitization of information exchange, however, also makes the practices of disinformation detectable, the networks of influence discernable, and suspicious content characterizable. New tools and approaches must be developed to leverage these affordances to understand and address this growing challenge.

cs.CY↗
arXiv2012

Inference in Hidden Markov Models with Explicit State Duration Distributions

In this letter we borrow from the inference techniques developed for unbounded state-cardinality (nonparametric) variants of the HMM and use them to develop a tuning-parameter free, black-box inference procedure for Explicit-state-duration hidden Markov models (EDHMM). EDHMMs are HMMs that have latent states consisting of both discrete state-indicator and discrete state-duration random variables. In contrast to the implicit geometric state duration distribution possessed by the standard HMM, EDHMMs allow the direct parameterisation and estimation of per-state duration distributions. As most duration distributions are defined over the positive integers, truncation or other approximations are usually required to perform EDHMM inference.

stat.ML↗
arXiv2005

ARACNE: An Algorithm for the Reconstruction of Gene Regulatory Networks in a Mammalian Cellular Context

Background: Elucidating gene regulatory networks is crucial for understanding normal cell physiology and complex pathologic phenotypes. Existing computational methods for the genome-wide ``reverse engineering'' of such networks have been successful only for lower eukaryotes with simple genomes. Here we present ARACNE, a novel algorithm, using microarray expression profiles, specifically designed to scale up to the complexity of regulatory networks in mammalian cells, yet general enough to address a wider range of network deconvolution problems. This method uses an information theoretic approach to eliminate the majority of indirect interactions inferred by co-expression methods. Results: We prove that ARACNE reconstructs the network exactly (asymptotically) if the effect of loops in the network topology is negligible, and we show that the algorithm works well in practice, even in the presence of numerous loops and complex topologies. We assess ARACNE's ability to reconstruct transcriptional regulatory networks using both a realistic synthetic dataset and a microarray dataset from human B cells. On synthetic datasets ARACNE achieves very low error rates and outperforms established methods, such as Relevance Networks and Bayesian Networks. Application to the deconvolution of genetic networks in human B cells demonstrates ARACNE's ability to infer validated transcriptional targets of the c MYC proto-oncogene. We also study the effects of mis estimation of mutual information on network reconstruction, and show that algorithms based on mutual information ranking are more resilient to estimation errors.

q-bio.MN↗
arXiv2005

Systematic identification of statistically significant network measures

We present a novel graph embedding space (i.e., a set of measures on graphs) for performing statistical analyses of networks. Key improvements over existing approaches include discovery of "motif-hubs" (multiple overlapping significant subgraphs), computational efficiency relative to subgraph census, and flexibility (the method is easily generalizable to weighted and signed graphs). The embedding space is based on {\it scalars}, functionals of the adjacency matrix representing the network. {\it Scalars} are global, involving all nodes; although they can be related to subgraph enumeration, there is not a one-to-one mapping between scalars and subgraphs. Improvements in network randomization and significance testing--we learn the distribution rather than assuming gaussianity--are also presented. The resulting algorithm establishes a systematic approach to the identification of the most significant scalars and suggests machine-learning techniques for network classification.

cond-mat.dis-nn↗
arXiv2004

An Information-Theoretic Approach to Network Modularity

Exploiting recent developments in information theory, we propose, illustrate, and validate a principled information-theoretic algorithm for module discovery and resulting measure of network modularity. This measure is an order parameter (a dimensionless number between 0 and 1). Comparison is made to other approaches to module-discovery and to quantifying network modularity using Monte Carlo generated Erdos-like modular networks. Finally, the Network Information Bottleneck (NIB) algorithm is applied to a number of real world networks, including the "social" network of coauthors at the APS March Meeting 2004.

q-bio.QM↗
arXiv2004

Predicting Genetic Regulatory Response Using Classification

We present a novel classification-based method for learning to predict gene regulatory response. Our approach is motivated by the hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can learn a decision rule for predicting whether a gene is up- or down-regulated in a particular experiment based on (1) the presence of binding site subsequences (``motifs'') in the gene's regulatory region and (2) the expression levels of regulators such as transcription factors in the experiment (``parents''). Thus our learning task integrates two qualitatively different data sources: genome-wide cDNA microarray data across multiple perturbation and mutant experiments along with motif profile data from regulatory sequences. We convert the regression task of predicting real-valued gene expression measurement to a classification task of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond the levels of biological and measurement noise in microarray measurements. The learning algorithm employed is boosting with a margin-based generalization of decision trees, alternating decision trees. This large-margin classifier is sufficiently flexible to allow complex logical functions, yet sufficiently simple to give insight into the combinatorial mechanisms of gene regulation. We observe encouraging prediction accuracy on experiments based on the Gasch S. cerevisiae dataset, and we show that we can accurately predict up- and down-regulation on held-out experiments. Our method thus provides predictive hypotheses, suggests biological experiments, and provides interpretable insight into the structure of genetic regulatory networks.

q-bio.QM↗
arXiv2004

Inferring Network Mechanisms: The Drosophila melanogaster Protein Interaction Network

Naturally occurring networks exhibit quantitative features revealing underlying growth mechanisms. Numerous network mechanisms have recently been proposed to reproduce specific properties such as degree distributions or clustering coefficients. We present a method for inferring the mechanism most accurately capturing a given network topology, exploiting discriminative tools from machine learning. The Drosophila melanogaster protein network is confidently and robustly (to noise and training data subsampling) classified as a duplication-mutation-complementation network over preferential attachment, small-world, and other duplication-mutation mechanisms. Systematic classification, rather than statistical study of specific properties, provides a discriminative approach to understand the design of complex networks.

q-bio.QM↗
arXiv2004

Predicting Genetic Regulatory Response using Classification: Yeast Stress Response

We present a novel classification-based algorithm called GeneClass for learning to predict gene regulatory response. Our approach is motivated by the hypothesis that in simple organisms such as Saccharomyces cerevisiae, we can learn a decision rule for predicting whether a gene is up- or down-regulated in a particular experiment based on (1) the presence of binding site subsequences (``motifs'') in the gene's regulatory region and (2) the expression levels of regulators such as transcription factors in the experiment (``parents''). Thus our learning task integrates two qualitatively different data sources: genome-wide cDNA microarray data across multiple perturbation and mutant experiments along with motif profile data from regulatory sequences. Rather than focusing on the regression task of predicting real-valued gene expression measurements, GeneClass performs the classification task of predicting +1 and -1 labels, corresponding to up- and down-regulation beyond the levels of biological and measurement noise in microarray measurements. GeneClass uses the Adaboost learning algorithm with a margin-based generalization of decision trees called alternating decision trees. In computational experiments based on the Gasch S. cerevisiae dataset, we show that the GeneClass method predicts up- and down-regulation on held-out experiments with high accuracy. We explore a range of experimental setups related to environmental stress response, and we retrieve important regulators, binding site motifs, and relationships between regulators and binding sites that are known to be associated to specific stress response pathways. Our method thus provides predictive hypotheses, suggests biological experiments, and provides interpretable insight into the structure of genetic regulatory networks.

q-bio.QM↗
arXiv2004

Discriminative Topological Features Reveal Biological Network Mechanisms

Recent genomic and bioinformatic advances have motivated the development of numerous random network models purporting to describe graphs of biological, technological, and sociological origin. The success of a model has been evaluated by how well it reproduces a few key features of the real-world data, such as degree distributions, mean geodesic lengths, and clustering coefficients. Often pairs of models can reproduce these features with indistinguishable fidelity despite being generated by vastly different mechanisms. In such cases, these few target features are insufficient to distinguish which of the different models best describes real world networks of interest; moreover, it is not clear a priori that any of the presently-existing algorithms for network generation offers a predictive description of the networks inspiring them. To derive discriminative classifiers, we construct a mapping from the set of all graphs to a high-dimensional (in principle infinite-dimensional) ``word space.'' This map defines an input space for classification schemes which allow us for the first time to state unambiguously which models are most descriptive of the networks they purport to describe. Our training sets include networks generated from 17 models either drawn from the literature or introduced in this work, source code for which is freely available. We anticipate that this new approach to network analysis will be of broad impact to a number of communities.

q-bio.MN↗
arXiv2002

Process Pathway Inference via Time Series Analysis

Motivated by recent experimental developments in functional genomics, we construct and test a numerical technique for inferring it process pathways, in which one process calls another process, from time series data. We validate using a case in which data are readily available and formulate an extension, appropriate for genetic regulatory networks, which exploits Bayesian inference and in which the present--day undersampling is compensated for by prior understanding of genetic regulation.

physics.bio-ph↗