Using PPI network autocorrelation in hierarchical multi-label classification trees for gene function prediction

BACKGROUND: Ontologies and catalogs of gene functions, such as the Gene Ontology (GO) and MIPS-FUN, assume that functional classes are organized hierarchically, that is, general functions include more specific ones. This has recently motivated the development of several machine learning algorithms for gene function prediction that leverages on this hierarchical organization where instances may belong to multiple classes. In addition, it is possible to exploit relationships among examples, since it is plausible that related genes tend to share functional annotations. Although these relationships have been identified and extensively studied in the area of protein-protein interaction (PPI) networks, they have not received much attention in hierarchical and multi-class gene function prediction. Relations between genes introduce autocorrelation in functional annotations and violate the assumption that instances are independently and identically distributed (i.i.d.), which underlines most machine learning algorithms. Although the explicit consideration of these relations brings additional complexity to the learning process, we expect substantial benefits in predictive accuracy of learned classifiers. RESULTS: This article demonstrates the benefits (in terms of predictive accuracy) of considering autocorrelation in multi-class gene function prediction. We develop a tree-based algorithm for considering network autocorrelation in the setting of Hierarchical Multi-label Classification (HMC). We empirically evaluate the proposed algorithm, called NHMC (Network Hierarchical Multi-label Classification), on 12 yeast datasets using each of the MIPS-FUN and GO annotation schemes and exploiting 2 different PPI networks. The results clearly show that taking autocorrelation into account improves the predictive performance of the learned models for predicting gene function. CONCLUSIONS: Our newly developed method for HMC takes into account network information in the learning phase: When used for gene function prediction in the context of PPI networks, the explicit consideration of network autocorrelation increases the predictive performance of the learned models. Overall, we found that this holds for different gene features/ descriptions, functional annotation schemes, and PPI networks: Best results are achieved when the PPI network is dense and contains a large proportion of function-relevant interactions

Method for Enabling Causal Inference in Relational Domains

The analysis of data from complex systems is quickly becoming a fundamental aspect of modern business, government, and science. The field of causal learning is concerned with developing a set of statistical methods that allow practitioners make inferences about unseen interventions. This field has seen significant advances in recent years. However, the vast majority of this work assumes that data instances are independent, whereas many systems are best described in terms of interconnected instances, i.e. relational systems. This discrepancy prevents causal inference techniques from being reliably applied in many real-world settings. In this thesis, I will present three contributions to the field of causal inference that seek to enable the analysis of relational systems. First, I will present theory for consistently testing statistical dependence in relational domains. I then show how the significance of this test can be measured in practice using a novel bootstrap method for structured domains. Second, I show that statistical dependence in relational domains is inherently asymmetric, implying a simple test of causal direction from observational data. This test requires no assumptions on either the marginal distributions of variables or the functional form of dependence. Third, I describe relational causal adjustment, a procedure to identify the effects of arbitrary interventions from observational relational data via an extension of Pearl\u27s backdoor criterion. A series of evaluations on synthetic domains shows the estimates obtained by relational causal adjustment are close to those obtained from explicit experimentation

A Shrinkage Approach for Modeling Non-Stationary Relational Autocorrelation

Recent research has shown that collective classification in relational data often exhibit significant performance gains over conventional approaches that classify instances individually. This is primarily due to the presence of autocorrelation in relational datasets, meaning that the class labels of related entities are correlated and inferences about one instance can be used to improve inferences about linked instances. Statistical relational learning techniques exploit relational autocorrelation by modeling global autocorrelation dependencies under the assumption that the level of autocorrelation is stationary throughout the dataset. To date, there has been no work examining the appropriateness of this stationarity assumption. In this paper; we examine two real-world datasets and show that there is significant variance in the autocorrelation dependencies throughout the relational data graphs. We develop a shrinkage technique for modeling this non-stationary autocorrelation and show that it achieves significant accuracy gains over competing techniques that model either local or global autocorrelation dependencies in isolation