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

Integrated Multi-omics Analysis Using Variational Autoencoders: Application to Pan-cancer Classification

Different aspects of a clinical sample can be revealed by multiple types of omics data. Integrated analysis of multi-omics data provides a comprehensive view of patients, which has the potential to facilitate more accurate clinical decision making. However, omics data are normally high dimensional with large number of molecular features and relatively small number of available samples with clinical labels. The "dimensionality curse" makes it challenging to train a machine learning model using high dimensional omics data like DNA methylation and gene expression profiles. Here we propose an end-to-end deep learning model called OmiVAE to extract low dimensional features and classify samples from multi-omics data. OmiVAE combines the basic structure of variational autoencoders with a classification network to achieve task-oriented feature extraction and multi-class classification. The training procedure of OmiVAE is comprised of an unsupervised phase without the classifier and a supervised phase with the classifier. During the unsupervised phase, a hierarchical cluster structure of samples can be automatically formed without the need for labels. And in the supervised phase, OmiVAE achieved an average classification accuracy of 97.49% after 10-fold cross-validation among 33 tumour types and normal samples, which shows better performance than other existing methods. The OmiVAE model learned from multi-omics data outperformed that using only one type of omics data, which indicates that the complementary information from different omics datatypes provides useful insights for biomedical tasks like cancer classification.Comment: 7 pages, 4 figure

Hierarchical Classification of Scientific Taxonomies with Autonomous Underwater Vehicles

Autonomous Underwater Vehicles (AUVs) have catalysed a significant shift in the way marine habitats are studied. It is now possible to deploy an AUV from a ship, and capture tens of thousands of georeferenced images in a matter of hours. There is a growing body of research investigating ways to automatically apply semantic labels to this data, with two goals. The task of manually labelling a large number of images is time consuming and error prone. Further, there is the potential to change AUV surveys from being geographically defined (based on a pre-planned route), to permitting the AUV to adapt the mission plan in response to semantic observations. This thesis focusses on frameworks that permit a unified machine learning approach with applicability to a wide range of geographic areas, and diverse areas of interest for marine scientists. This can be addressed through the use of hierarchical classification; in which machine learning algorithms are trained to predict not just a binary or multi-class outcome, but a hierarchy of related output labels which are not mutually exclusive, such as a scientific taxonomy. In order to investigate classification on larger hierarchies with greater geographic diversity, the BENTHOZ-2015 data set was assembled as part of a collaboration between five Australian research groups. Existing labelled data was re-mapped to the CATAMI hierarchy, in total more than 400,000 point labels, conforming to a hierarchy of around 150 classes. The common hierarchical classification approach of building a network of binary classifiers was applied to the BENTHOZ-2015 data set, and a novel application of Bayesian Network theory and probability calibration was used as a theoretical foundation for the approach, resulting in improved classifier performance. This was extended to a more complex hidden node Bayesian Network structure, which permits inclusion of additional sensor modalities, and tuning for better performance in particular geographic regions

Novel approaches for hierarchical classification with case studies in protein function prediction

A very large amount of research in the data mining, machine learning, statistical pattern recognition and related research communities has focused on flat classification problems. However, many problems in the real world such as hierarchical protein function prediction have their classes naturally organised into hierarchies. The task of hierarchical classification, however, needs to be better defined as researchers into one application domain are often unaware of similar efforts developed in other research areas. The first contribution of this thesis is to survey the task of hierarchical classification across different application domains and present an unifying framework for the task. After clearly defining the problem, we explore novel approaches to the task. Based on the understanding gained by surveying the task of hierarchical classification, there are three major approaches to deal with hierarchical classification problems. The first approach is to use one of the many existing flat classification algorithms to predict only the leaf classes in the hierarchy. Note that, in the training phase, this approach completely ignores the hierarchical class relationships, i.e. the parent-child and sibling class relationships, but in the testing phase the ancestral classes of an instance can be inferred from its predicted leaf classes. The second approach is to build a set of local models, by training one flat classification algorithm for each local view of the hierarchy. The two main variations of this approach are: (a) training a local flat multi-class classifier at each non-leaf class node, where each classifier discriminates among the child classes of its associated class; or (b) training a local fiat binary classifier at each node of the class hierarchy, where each classifier predicts whether or not a new instance has the classifier’s associated class. In both these variations, in the testing phase a procedure is used to combine the predictions of the set of local classifiers in a coherent way, avoiding inconsistent predictions. The third approach is to use a global-model hierarchical classification algorithm, which builds one single classification model by taking into account all the hierarchical class relationships in the training phase. In the context of this categorization of hierarchical classification approaches, the other contributions of this thesis are as follows. The second contribution of this thesis is a novel algorithm which is based on the local classifier per parent node approach. The novel algorithm is the selective representation approach that automatically selects the best protein representation to use at each non-leaf class node. The third contribution is a global-model hierarchical classification extension of the well known naive Bayes algorithm. Given the good predictive performance of the global-model hierarchical-classification naive Bayes algorithm, we relax the Naive Bayes’ assumption that attributes are independent from each other given the class by using the concept of k dependencies. Hence, we extend the flat classification /¿-Dependence Bayesian network classifier to the task of hierarchical classification, which is the fourth contribution of this thesis. Both the proposed global-model hierarchical classification Naive Bayes and the proposed global-model hierarchical /¿-Dependence Bayesian network classifier have achieved predictive accuracies that were, overall, significantly higher than the predictive accuracies obtained by their corresponding local hierarchical classification versions, across a number of datasets for the task of hierarchical protein function prediction

Effectiveness of Hierarchical Softmax in Large Scale Classification Tasks

Typically, Softmax is used in the final layer of a neural network to get a probability distribution for output classes. But the main problem with Softmax is that it is computationally expensive for large scale data sets with large number of possible outputs. To approximate class probability efficiently on such large scale data sets we can use Hierarchical Softmax. LSHTC datasets were used to study the performance of the Hierarchical Softmax. LSHTC datasets have large number of categories. In this paper we evaluate and report the performance of normal Softmax Vs Hierarchical Softmax on LSHTC datasets. This evaluation used macro f1 score as a performance measure. The observation was that the performance of Hierarchical Softmax degrades as the number of classes increase