A transversal approach to predict gene product networks from ontology-based similarity

<p>Abstract</p> <p>Background</p> <p>Interpretation of transcriptomic data is usually made through a "standard" approach which consists in clustering the genes according to their expression patterns and exploiting Gene Ontology (GO) annotations within each expression cluster. This approach makes it difficult to underline functional relationships between gene products that belong to different expression clusters. To address this issue, we propose a transversal analysis that aims to predict functional networks based on a combination of GO processes and data expression.</p> <p>Results</p> <p>The transversal approach presented in this paper consists in computing the semantic similarity between gene products in a Vector Space Model. Through a weighting scheme over the annotations, we take into account the representativity of the terms that annotate a gene product. Comparing annotation vectors results in a matrix of gene product similarities. Combined with expression data, the matrix is displayed as a set of functional gene networks. The transversal approach was applied to 186 genes related to the enterocyte differentiation stages. This approach resulted in 18 functional networks proved to be biologically relevant. These results were compared with those obtained through a standard approach and with an approach based on information content similarity.</p> <p>Conclusion</p> <p>Complementary to the standard approach, the transversal approach offers new insight into the cellular mechanisms and reveals new research hypotheses by combining gene product networks based on semantic similarity, and data expression.</p

Network Analysis on Incomplete Structures.

Over the past decade, networks have become an increasingly popular abstraction for problems in the physical, life, social and information sciences. Network analysis can be used to extract insights into an underlying system from the structure of its network representation. One of the challenges of applying network analysis is the fact that networks do not always have an observed and complete structure. This dissertation focuses on the problem of imputation and/or inference in the presence of incomplete network structures. I propose four novel systems, each of which, contain a module that involves the inference or imputation of an incomplete network that is necessary to complete the end task. I first propose EdgeBoost, a meta-algorithm and framework that repeatedly applies a non-deterministic link predictor to improve the efficacy of community detection algorithms on networks with missing edges. On average EdgeBoost improves performance of existing algorithms by 7% on artificial data and 17% on ego networks collected from Facebook. The second system, Butterworth, identifies a social network user's topic(s) of interests and automatically generates a set of social feed ``rankers'' that enable the user to see topic specific sub-feeds. Butterworth uses link prediction to infer the missing semantics between members of a user's social network in order to detect topical clusters embedded in the network structure. For automatically generated topic lists, Butterworth achieves an average top-10 precision of 78%, as compared to a time-ordered baseline of 45%. Next, I propose Dobby, a system for constructing a knowledge graph of user-defined keyword tags. Leveraging a sparse set of labeled edges, Dobby trains a supervised learning algorithm to infer the hypernym relationships between keyword tags. Dobby was evaluated by constructing a knowledge graph of LinkedIn's skills dataset, achieving an average precision of 85% on a set of human labeled hypernym edges between skills. Lastly, I propose Lobbyback, a system that automatically identifies clusters of documents that exhibit text reuse and generates ``prototypes'' that represent a canonical version of text shared between the documents. Lobbyback infers a network structure in a corpus of documents and uses community detection in order to extract the document clusters.PhDComputer Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/133443/1/mattburg_1.pd

Theory and Applications for Advanced Text Mining

Due to the growth of computer technologies and web technologies, we can easily collect and store large amounts of text data. We can believe that the data include useful knowledge. Text mining techniques have been studied aggressively in order to extract the knowledge from the data since late 1990s. Even if many important techniques have been developed, the text mining research field continues to expand for the needs arising from various application fields. This book is composed of 9 chapters introducing advanced text mining techniques. They are various techniques from relation extraction to under or less resourced language. I believe that this book will give new knowledge in the text mining field and help many readers open their new research fields

Ontology based data warehousing for mining of heterogeneous and multidimensional data sources

Heterogeneous and multidimensional big-data sources are virtually prevalent in all business environments. System and data analysts are unable to fast-track and access big-data sources. A robust and versatile data warehousing system is developed, integrating domain ontologies from multidimensional data sources. For example, petroleum digital ecosystems and digital oil field solutions, derived from big-data petroleum (information) systems, are in increasing demand in multibillion dollar resource businesses worldwide. This work is recognized by Industrial Electronic Society of IEEE and appeared in more than 50 international conference proceedings and journals

Knowledge-based Biomedical Data Science 2019

Knowledge-based biomedical data science (KBDS) involves the design and implementation of computer systems that act as if they knew about biomedicine. Such systems depend on formally represented knowledge in computer systems, often in the form of knowledge graphs. Here we survey the progress in the last year in systems that use formally represented knowledge to address data science problems in both clinical and biological domains, as well as on approaches for creating knowledge graphs. Major themes include the relationships between knowledge graphs and machine learning, the use of natural language processing, and the expansion of knowledge-based approaches to novel domains, such as Chinese Traditional Medicine and biodiversity.Comment: Manuscript 43 pages with 3 tables; Supplemental material 43 pages with 3 table

Epithelial specific transcriptome map of the human prostate

The prostate has a zonal anatomy, with differing susceptibilities to disease (benign prostatic hyperplasia originates from the transition zone, prostate cancer largely arises in the peripheral zone). The molecular reasons for this are not understood. Previous prostate cancer microarray studies have used whole benign, diseased or tissue adjacent to the carcinoma as normal controls, for what is an epithelial disease. This study provides a gene expression profile of normal, non-diseased prostate, or a ‘reference prostate gene expression profile’. This has been compared to prostate cancer to identify novel biomarkers of disease. This study also investigates zonal differences in gene expression between different anatomical zones of the prostate. I used normal, human donor prostate tissue, laser capture microdissection (LCM), and Affymetrix gene expression arrays to achieve these aims. Eight LCM prostate epithelial samples from 3 donor prostates were used. The gene expression data was validated by low density real-time PCR and immunohistochemistry on a prostate tissue microarray. Major differences in gene expression were discovered between whole tissue and LCM epithelium only prostate using homology tables. Novel prostate adenocarcinoma genes were identified using a publicly available LCM prostate cancer gene expression array dataset. 9318 genes showed significant differential expression in normal vs. cancer datasets. Three targets, MCM2, NR1D1 and ABCA1 were validated at the protein level. Expression of NR1D1 and ABCA1 were increased in cancer, suggesting they are novel epithelial biomarkers of prostate cancer. An analysis of zonal differences in gene expression found significant differences between zones. Zonal specific markers included TGM4 (central zone), LPL (peripheral zone), and COL9A1 (transition zone). This study provides: (i) a gene expression profile of the normal prostate epithelium (ii) novel, prostate adenocarcinoma specific gene and protein markers and (iii) the first gene expression profile of normal epithelium on the basis of zonal anatomy of the prostate

Investigating “Gene Ontology”- based semantic similarity in the context of functional genomics

Gene functional annotations are an essential part of knowledge discovery in the analysis of large datasets, with the Gene Ontology [Ashburner et al., 2000] as the de facto standard for such annotations. A considerable number of approaches for quantifying functional similarity between gene products based on the semantic similarity between their annotations have been developed, but little guidance exists as to which of these measures are the most appropriate for different purposes. This was addressed here by comparing the performances of a number of similarity measures and associated parameters. This comparison provided some interesting new insights as well as confirming emerging trends from the literature. There is also a pressing need for novel ways of applying these measures to facilitate the functional analysis of lists of gene products. We developed a novel algorithm, FuSiGroups, to group GO terms based on their semantic similarity and genes based on their functional similarity. This two-fold grouping results in groups of not only functionally similar genes but also an associated set of related GO terms that characterise a single functional aspect relating the genes in the group, which facilitates analysis by creating more coherent groups. Each gene can belong to multiple groups, so the groups more accurately reflect the complexity of biological reality than clusters generated using traditional approaches. FuSiGroups was tested on a number of scenarios and in each case, successfully generated biologically relevant groups, identifying the key functional aspects of the dataset. The algorithm also managed to eliminate genes that were functionally unrelated to the bulk of the dataset and distinguish between different biological pathways. Although dataset size is currently a limiting factor, with smaller datasets performing the best, FuSiGroups has been demonstrated as a promising approach for the functional analysis of gene products.EThOS - Electronic Theses Online ServiceGBUnited Kingdo