Gene Tree Labeling Using Nonnegative Matrix Factorization on Biomedical Literature

Identifying functional groups of genes is a challenging problem for biological applications. Text mining approaches can be used to build hierarchical clusters or trees from the information in the biological literature. In particular, the nonnegative matrix factorization (NMF) is examined as one approach to label hierarchical trees. A generic labeling algorithm as well as an evaluation technique is proposed, and the effects of different NMF parameters with regard to convergence and labeling accuracy are discussed. The primary goals of this study are to provide a qualitative assessment of the NMF and its various parameters and initialization, to provide an automated way to classify biomedical data, and to provide a method for evaluating labeled data assuming a static input tree. As a byproduct, a method for generating gold standard trees is proposed

Automated Gene Classification using Nonnegative Matrix Factorization on Biomedical Literature

Understanding functional gene relationships is a challenging problem for biological applications. High-throughput technologies such as DNA microarrays have inundated biologists with a wealth of information, however, processing that information remains problematic. To help with this problem, researchers have begun applying text mining techniques to the biological literature. This work extends previous work based on Latent Semantic Indexing (LSI) by examining Nonnegative Matrix Factorization (NMF). Whereas LSI incorporates the singular value decomposition (SVD) to approximate data in a dense, mixed-sign space, NMF produces a parts-based factorization that is directly interpretable. This space can, in theory, be used to augment existing ontologies and annotations by identifying themes within the literature. Of course, performing NMF does not come without a price—namely, the large number of parameters. This work attempts to analyze the effects of some of the NMF parameters on both convergence and labeling accuracy. Since there is a dearth of automated label evaluation techniques as well as “gold standard” hierarchies, a method to produce “correct” trees is proposed as well as a technique to label trees and to evaluate those labels

Discovering gene functional relationships using FAUN (Feature Annotation Using Nonnegative matrix factorization)

Background Searching the enormous amount of information available in biomedical literature to extract novel functional relationships among genes remains a challenge in the field of bioinformatics. While numerous (software) tools have been developed to extract and identify gene relationships from biological databases, few effectively deal with extracting new (or implied) gene relationships, a process which is useful in interpretation of discovery-oriented genome-wide experiments. Results In this study, we develop a Web-based bioinformatics software environment called FAUN or Feature Annotation Using Nonnegative matrix factorization (NMF) to facilitate both the discovery and classification of functional relationships among genes. Both the computational complexity and parameterization of NMF for processing gene sets are discussed. FAUN is tested on three manually constructed gene document collections. Its utility and performance as a knowledge discovery tool is demonstrated using a set of genes associated with Autism. Conclusions FAUN not only assists researchers to use biomedical literature efficiently, but also provides utilities for knowledge discovery. This Web-based software environment may be useful for the validation and analysis of functional associations in gene subsets identified by high-throughput experiments

Discovering gene functional relationships using a literature-based NMF model

The rapid growth of the biomedical literature and genomic information presents a major challenge for determining the functional relationships among genes. Several bioinformatics tools have been developed to extract and identify gene relationships from various biological databases. However, an intuitive user-interface tool that allows the biologist to determine functional relationships among genes is still not available. In this study, we develop a Web-based bioinformatics software environment called FAUN or Feature Annotation Using Nonnegative matrix factorization (NMF) to facilitate both the discovery and classification of functional relationships among genes. Both the computational complexity and parameterization of NMF for processing gene sets are discussed. We tested FAUN on three manually constructed gene document collections, and then used it to analyze several microarray-derived gene sets obtained from studies of the developing cerebellum in normal and mutant mice. FAUN provides utilities for collaborative knowledge discovery and identification of new gene relationships from text streams and repositories (e.g., MEDLINE). It is particularly useful for the validation and analysis of gene associations suggested by microarray experimentation. The FAUN site is publicly available at http://grits.eecs.utk.edu/faun

SENT: semantic features in text

We present SENT (semantic features in text), a functional interpretation tool based on literature analysis. SENT uses Non-negative Matrix Factorization to identify topics in the scientific articles related to a collection of genes or their products, and use them to group and summarize these genes. In addition, the application allows users to rank and explore the articles that best relate to the topics found, helping put the analysis results into context. This approach is useful as an exploratory step in the workflow of interpreting and understanding experimental data, shedding some light into the complex underlying biological mechanisms. This tool provides a user-friendly interface via a web site, and a programmatic access via a SOAP web server. SENT is freely accessible at http://sent.dacya.ucm.es

A Visual Approach to Automated Text Mining and Knowledge Discovery

The focus of this dissertation has been on improving the non-negative tensor factorization technique of text mining. The improvements have been made in both pre-processing and post-processing stages, with the goal of making the non-negative tensor factorization algorithm accessible to the casual user. The improved implementation allows the user to construct and modify the contents of the tensor, experiment with relative term weights and trust measures, and experiment with the total number of algorithm output features. Non-negative tensor factorization output feature production is closely integrated with a visual post-processing tool, FutureLens, that allows the user to perform in depth analysis and has a great potential for discovery of interesting and novel patterns within a large collection of textual data. This dissertation necessitated a number of significant modifications and additions to FutureLens in order to facilitate its integration into the analysis environment

Relation Prediction over Biomedical Knowledge Bases for Drug Repositioning

Identifying new potential treatment options for medical conditions that cause human disease burden is a central task of biomedical research. Since all candidate drugs cannot be tested with animal and clinical trials, in vitro approaches are first attempted to identify promising candidates. Likewise, identifying other essential relations (e.g., causation, prevention) between biomedical entities is also critical to understand biomedical processes. Hence, it is crucial to develop automated relation prediction systems that can yield plausible biomedical relations to expedite the discovery process. In this dissertation, we demonstrate three approaches to predict treatment relations between biomedical entities for the drug repositioning task using existing biomedical knowledge bases. Our approaches can be broadly labeled as link prediction or knowledge base completion in computer science literature. Specifically, first we investigate the predictive power of graph paths connecting entities in the publicly available biomedical knowledge base, SemMedDB (the entities and relations constitute a large knowledge graph as a whole). To that end, we build logistic regression models utilizing semantic graph pattern features extracted from the SemMedDB to predict treatment and causative relations in Unified Medical Language System (UMLS) Metathesaurus. Second, we study matrix and tensor factorization algorithms for predicting drug repositioning pairs in repoDB, a general purpose gold standard database of approved and failed drug–disease indications. The idea here is to predict repoDB pairs by approximating the given input matrix/tensor structure where the value of a cell represents the existence of a relation coming from SemMedDB and UMLS knowledge bases. The essential goal is to predict the test pairs that have a blank cell in the input matrix/tensor based on the shared biomedical context among existing non-blank cells. Our final approach involves graph convolutional neural networks where entities and relation types are embedded in a vector space involving neighborhood information. Basically, we minimize an objective function to guide our model to concept/relation embeddings such that distance scores for positive relation pairs are lower than those for the negative ones. Overall, our results demonstrate that recent link prediction methods applied to automatically curated, and hence imprecise, knowledge bases can nevertheless result in high accuracy drug candidate prediction with appropriate configuration of both the methods and datasets used

Innovative Algorithms and Evaluation Methods for Biological Motif Finding

Biological motifs are defined as overly recurring sub-patterns in biological systems. Sequence motifs and network motifs are the examples of biological motifs. Due to the wide range of applications, many algorithms and computational tools have been developed for efficient search for biological motifs. Therefore, there are more computationally derived motifs than experimentally validated motifs, and how to validate the biological significance of the ‘candidate motifs’ becomes an important question. Some of sequence motifs are verified by their structural similarities or their functional roles in DNA or protein sequences, and stored in databases. However, biological role of network motifs is still invalidated and currently no databases exist for this purpose. In this thesis, we focus not only on the computational efficiency but also on the biological meanings of the motifs. We provide an efficient way to incorporate biological information with clustering analysis methods: For example, a sparse nonnegative matrix factorization (SNMF) method is used with Chou-Fasman parameters for the protein motif finding. Biological network motifs are searched by various clustering algorithms with Gene ontology (GO) information. Experimental results show that the algorithms perform better than existing algorithms by producing a larger number of high-quality of biological motifs. In addition, we apply biological network motifs for the discovery of essential proteins. Essential proteins are defined as a minimum set of proteins which are vital for development to a fertile adult and in a cellular life in an organism. We design a new centrality algorithm with biological network motifs, named MCGO, and score proteins in a protein-protein interaction (PPI) network to find essential proteins. MCGO is also combined with other centrality measures to predict essential proteins using machine learning techniques. We have three contributions to the study of biological motifs through this thesis; 1) Clustering analysis is efficiently used in this work and biological information is easily integrated with the analysis; 2) We focus more on the biological meanings of motifs by adding biological knowledge in the algorithms and by suggesting biologically related evaluation methods. 3) Biological network motifs are successfully applied to a practical application of prediction of essential proteins

Data Clustering And Visualization Through Matrix Factorization

Clustering is traditionally an unsupervised task which is to find natural groupings or clusters in multidimensional data based on perceived similarities among the patterns. The purpose of clustering is to extract useful information from unlabeled data. In order to present the extracted useful knowledge obtained by clustering in a meaningful way, data visualization becomes a popular and growing area of research field. Visualization can provide a qualitative overview of large and complex data sets, which help us the desired insight in truly understanding the phenomena of interest in data. The contribution of this dissertation is two-fold: Semi-Supervised Non-negative Matrix Factorization (SS-NMF) for data clustering/co-clustering and Exemplar-based data Visualization (EV) through matrix factorization. Compared to traditional data mining models, matrix-based methods are fast, easy to understand and implement, especially suitable to solve large-scale challenging problems in text mining, image grouping, medical diagnosis, and bioinformatics. In this dissertation, we present two effective matrix-based solutions in the new directions of data clustering and visualization. First, in many practical learning domains, there is a large supply of unlabeled data but limited labeled data, and in most cases it might be expensive to generate large amounts of labeled data. Traditional clustering algorithms completely ignore these valuable labeled data and thus are inapplicable to these problems. Consequently, semi-supervised clustering, which can incorporate the domain knowledge to guide a clustering algorithm, has become a topic of significant recent interest. Thus, we develop a Non-negative Matrix Factorization (NMF) based framework to incorporate prior knowledge into data clustering. Moreover, with the fast growth of Internet and computational technologies in the past decade, many data mining applications have advanced swiftly from the simple clustering of one data type to the co-clustering of multiple data types, usually involving high heterogeneity. To this end, we extend SS-NMF to perform heterogeneous data co-clustering. From a theoretical perspective, SS-NMF for data clustering/co-clustering is mathematically rigorous. The convergence and correctness of our algorithms are proved. In addition, we discuss the relationship between SS-NMF with other well-known clustering and co-clustering models. Second, most of current clustering models only provide the centroids (e.g., mathematical means of the clusters) without inferring the representative exemplars from real data, thus they are unable to better summarize or visualize the raw data. A new method, Exemplar-based Visualization (EV), is proposed to cluster and visualize an extremely large-scale data. Capitalizing on recent advances in matrix approximation and factorization, EV provides a means to visualize large scale data with high accuracy (in retaining neighbor relations), high efficiency (in computation), and high flexibility (through the use of exemplars). Empirically, we demonstrate the superior performance of our matrix-based data clustering and visualization models through extensive experiments performed on the publicly available large scale data sets

Unsupervised Algorithms for Microarray Sample Stratification

The amount of data made available by microarrays gives researchers the opportunity to delve into the complexity of biological systems. However, the noisy and extremely high-dimensional nature of this kind of data poses significant challenges. Microarrays allow for the parallel measurement of thousands of molecular objects spanning different layers of interactions. In order to be able to discover hidden patterns, the most disparate analytical techniques have been proposed. Here, we describe the basic methodologies to approach the analysis of microarray datasets that focus on the task of (sub)group discovery.Peer reviewe