arXiv subjects

David Page

Publications and source records attributed to David Page.

29 records · Page 2Linked to original sources

arXiv2019

Machine Learning to Predict Developmental Neurotoxicity with High-throughput Data from 2D Bio-engineered Tissues

There is a growing need for fast and accurate methods for testing developmental neurotoxicity across several chemical exposure sources. Current approaches, such as in vivo animal studies, and assays of animal and human primary cell cultures, suffer from challenges related to time, cost, and applicability to human physiology. We previously demonstrated success employing machine learning to predict developmental neurotoxicity using gene expression data collected from human 3D tissue models exposed to various compounds. The 3D model is biologically similar to developing neural structures, but its complexity necessitates extensive expertise and effort to employ. By instead focusing solely on constructing an assay of developmental neurotoxicity, we propose that a simpler 2D tissue model may prove sufficient. We thus compare the accuracy of predictive models trained on data from a 2D tissue model with those trained on data from a 3D tissue model, and find the 2D model to be substantially more accurate. Furthermore, we find the 2D model to be more robust under stringent gene set selection, whereas the 3D model suffers substantial accuracy degradation. While both approaches have advantages and disadvantages, we propose that our described 2D approach could be a valuable tool for decision makers when prioritizing neurotoxicity screening.

q-bio.QM↗

arXiv2018

Privacy-Preserving Collaborative Prediction using Random Forests

We study the problem of privacy-preserving machine learning (PPML) for ensemble methods, focusing our effort on random forests. In collaborative analysis, PPML attempts to solve the conflict between the need for data sharing and privacy. This is especially important in privacy sensitive applications such as learning predictive models for clinical decision support from EHR data from different clinics, where each clinic has a responsibility for its patients' privacy. We propose a new approach for ensemble methods: each entity learns a model, from its own data, and then when a client asks the prediction for a new private instance, the answers from all the locally trained models are used to compute the prediction in such a way that no extra information is revealed. We implement this approach for random forests and we demonstrate its high efficiency and potential accuracy benefit via experiments on real-world datasets, including actual EHR data.

cs.LG↗

arXiv2018

An Inductive Logic Programming Approach to Validate Hexose Binding Biochemical Knowledge

Hexoses are simple sugars that play a key role in many cellular pathways, and in the regulation of development and disease mechanisms. Current protein-sugar computational models are based, at least partially, on prior biochemical findings and knowledge. They incorporate different parts of these findings in predictive black-box models. We investigate the empirical support for biochemical findings by comparing Inductive Logic Programming (ILP) induced rules to actual biochemical results. We mine the Protein Data Bank for a representative data set of hexose binding sites, non-hexose binding sites and surface grooves. We build an ILP model of hexose-binding sites and evaluate our results against several baseline machine learning classifiers. Our method achieves an accuracy similar to that of other black-box classifiers while providing insight into the discriminating process. In addition, it confirms wet-lab findings and reveals a previously unreported Trp-Glu amino acids dependency.

q-bio.OT↗

arXiv2017

An Efficient Pseudo-likelihood Method for Sparse Binary Pairwise Markov Network Estimation

The pseudo-likelihood method is one of the most popular algorithms for learning sparse binary pairwise Markov networks. In this paper, we formulate the $L_1$ regularized pseudo-likelihood problem as a sparse multiple logistic regression problem. In this way, many insights and optimization procedures for sparse logistic regression can be applied to the learning of discrete Markov networks. Specifically, we use the coordinate descent algorithm for generalized linear models with convex penalties, combined with strong screening rules, to solve the pseudo-likelihood problem with $L_1$ regularization. Therefore a substantial speedup without losing any accuracy can be achieved. Furthermore, this method is more stable than the node-wise logistic regression approach on unbalanced high-dimensional data when penalized by small regularization parameters. Thorough numerical experiments on simulated data and real world data demonstrate the advantages of the proposed method.

stat.ML↗

arXiv2016

Computational Drug Repositioning Using Continuous Self-controlled Case Series

Computational Drug Repositioning (CDR) is the task of discovering potential new indications for existing drugs by mining large-scale heterogeneous drug-related data sources. Leveraging the patient-level temporal ordering information between numeric physiological measurements and various drug prescriptions provided in Electronic Health Records (EHRs), we propose a Continuous Self-controlled Case Series (CSCCS) model for CDR. As an initial evaluation, we look for drugs that can control Fasting Blood Glucose (FBG) level in our experiments. Applying CSCCS to the Marshfield Clinic EHR, well-known drugs that are indicated for controlling blood glucose level are rediscovered. Furthermore, some drugs with recent literature support for the potential effect of blood glucose level control are also identified.

stat.AP↗

arXiv2012

CLP(BN): Constraint Logic Programming for Probabilistic Knowledge

We present CLP(BN), a novel approach that aims at expressing Bayesian networks through the constraint logic programming framework. Arguably, an important limitation of traditional Bayesian networks is that they are propositional, and thus cannot represent relations between multiple similar objects in multiple contexts. Several researchers have thus proposed first-order languages to describe such networks. Namely, one very successful example of this approach are the Probabilistic Relational Models (PRMs), that combine Bayesian networks with relational database technology. The key difficulty that we had to address when designing CLP(cal{BN}) is that logic based representations use ground terms to denote objects. With probabilitic data, we need to be able to uniquely represent an object whose value we are not sure about. We use {sl Skolem functions} as unique new symbols that uniquely represent objects with unknown value. The semantics of CLP(cal{BN}) programs then naturally follow from the general framework of constraint logic programming, as applied to a specific domain where we have probabilistic data. This paper introduces and defines CLP(cal{BN}), and it describes an implementation and initial experiments. The paper also shows how CLP(cal{BN}) relates to Probabilistic Relational Models (PRMs), Ngo and Haddawys Probabilistic Logic Programs, AND Kersting AND De Raedts Bayesian Logic Programs.

cs.AI↗

arXiv2012

Graphical-model Based Multiple Testing under Dependence, with Applications to Genome-wide Association Studies

Large-scale multiple testing tasks often exhibit dependence, and leveraging the dependence between individual tests is still one challenging and important problem in statistics. With recent advances in graphical models, it is feasible to use them to perform multiple testing under dependence. We propose a multiple testing procedure which is based on a Markov-random-field-coupled mixture model. The ground truth of hypotheses is represented by a latent binary Markov random field, and the observed test statistics appear as the coupled mixture variables. The parameters in our model can be automatically learned by a novel EM algorithm. We use an MCMC algorithm to infer the posterior probability that each hypothesis is null (termed local index of significance), and the false discovery rate can be controlled accordingly. Simulations show that the numerical performance of multiple testing can be improved substantially by using our procedure. We apply the procedure to a real-world genome-wide association study on breast cancer, and we identify several SNPs with strong association evidence.

stat.ME↗

arXiv2012

Unachievable Region in Precision-Recall Space and Its Effect on Empirical Evaluation

Precision-recall (PR) curves and the areas under them are widely used to summarize machine learning results, especially for data sets exhibiting class skew. They are often used analogously to ROC curves and the area under ROC curves. It is known that PR curves vary as class skew changes. What was not recognized before this paper is that there is a region of PR space that is completely unachievable, and the size of this region depends only on the skew. This paper precisely characterizes the size of that region and discusses its implications for empirical evaluation methodology in machine learning.

cs.LG↗

arXiv2012

Demand-Driven Clustering in Relational Domains for Predicting Adverse Drug Events

Learning from electronic medical records (EMR) is challenging due to their relational nature and the uncertain dependence between a patient's past and future health status. Statistical relational learning is a natural fit for analyzing EMRs but is less adept at handling their inherent latent structure, such as connections between related medications or diseases. One way to capture the latent structure is via a relational clustering of objects. We propose a novel approach that, instead of pre-clustering the objects, performs a demand-driven clustering during learning. We evaluate our algorithm on three real-world tasks where the goal is to use EMRs to predict whether a patient will have an adverse reaction to a medication. We find that our approach is more accurate than performing no clustering, pre-clustering, and using expert-constructed medical heterarchies.

cs.LG↗

arXiv2012

Learning Bayesian Network Structure from Correlation-Immune Data

Searching the complete space of possible Bayesian networks is intractable for problems of interesting size, so Bayesian network structure learning algorithms, such as the commonly used Sparse Candidate algorithm, employ heuristics. However, these heuristics also restrict the types of relationships that can be learned exclusively from data. They are unable to learn relationships that exhibit "correlation-immunity", such as parity. To learn Bayesian networks in the presence of correlation-immune relationships, we extend the Sparse Candidate algorithm with a technique called "skewing". This technique uses the observation that relationships that are correlation-immune under a specific input distribution may not be correlation-immune under another, sufficiently different distribution. We show that by extending Sparse Candidate with this technique we are able to discover relationships between random variables that are approximately correlation-immune, with a significantly lower computational cost than the alternative of considering multiple parents of a node at a time.

cs.AI↗

arXiv2008

Phases Of N=2 Theories In 1+1 Dimensions With Boundary

We study B-type D-branes in linear sigma models with Abelian gauge groups. The most important finding is the grade restriction rule. It classifies representations of the gauge group on the Chan-Paton factor, which can be used to define a family of D-branes over a region of the Kähler moduli space that connects special points of different character. As an application, we find a precise, transparent relation between D-branes in various geometric phases as well as free orbifold and Landau-Ginzburg points. The result reproduces and unifies many of the earlier mathematical results on equivalences of D-brane categories, including the McKay correspondence and Orlov's construction.

hep-th↗