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    Bioinformatics tools and explainable machine learning approaches for colorectal cancer genomic and metagenomic data analysis : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Computer Science, School of Mathematical and Computational Sciences at Massey University, Albany Campus, Auckland, New Zealand

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    Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide and is influenced by complex interactions between genetic factors and the microbiome. The advent of high-throughput sequencing technologies has led to the generation of vast amounts of genomic and metagenomic data, providing opportunities to uncover novel biological markers (biomarkers) for CRC diagnosis, prognosis, and treatment. However, analyzing such datasets poses significant computational and interpretive challenges, necessitating the development of efficient and user-friendly bioinformatics tools. Recent advancements in machine learning, particularly Random Forest (RF) models, have shown promise in identifying predictive features in genomic data. Yet, existing implementations often face limitations in scaling and interpretability, especially when applied to large genomic studies. Additionally, integrating host genomic and microbial metagenomic data remains a complex task due to the heterogeneity of data types and sophisticated analytical methods required. This thesis focuses on the development of computational tools and the application of machine learning techniques to enhance the analysis of genomic and metagenomic data for colorectal cancer research. Firstly, I present the MetaFunc App, an interactive Shiny application designed to facilitate the exploration of data generated from the MetaFunc pipeline, an analysis pipeline for host and microbiome transcriptome data. The app provides a user-friendly interface for visualizing and analyzing microbial taxonomic profiles alongside host gene expression data, linking functional annotations to specific microbial taxa. This integration facilitates a deeper understanding of microbial contributions to a designated target outcome, e.g. cancer versus normal, and aids in identifying potential microbial biomarkers and eliciting their functions. Secondly, I apply Random Forest machine learning models to identify genomic and microbial biomarkers that differentiate right-sided colorectal cancer (RCC) from left-sided colorectal cancer (LCC). Utilizing RNA-seq data for 58,677 coding and non-coding human genes, and count data for 28,577 microbial taxa from 308 patient tumour samples, I develop three models: a genes-only model, a microbes-only model, and a combined genes-and-microbes model. The genes-only model achieves an accuracy of 90%, identifying significant genomic features such as PRAC1, HOXB13, HOXC4, and HOXC6, which are associated with colorectal cancer location and development. The microbes-only model achieves an accuracy of 70%, identifying significant microbial features including Ruminococcus gnavus and Fusobacterium nucleatum. The combined model achieves an accuracy of 87%, which may reflect an association between microbial communities and host gene expression in CRC. Finally, I present pyRforest, an R package that integrates Python’s scikit-learn RandomForestClassifier into the R environment via the reticulate package to enhance computational efficiency and memory management when using Random Forest models in R to analyze large genomic datasets. pyRforest also includes a novel rank-based permutation method for calculating p-values of individual features for feature identification. Additionally, it includes the capacity for calculating and plotting SHapley Additive exPlanations (SHAP) to interpret the contribution of each feature to model predictions, enhancing the explainability of Random Forest model results. The utility of pyRforest is demonstrated through a case study, where it is used to identify candidate biomarkers and provide insights into biological significance. Collectively, this work advances the understanding of genomic and microbial factors influencing colorectal cancer and provides advanced computational tools that can be used in other analyses. The MetaFunc App and pyRforest package facilitate the integration and interpretation of complex genomic and metagenomic data, and represent valuable resources for biomarker discovery. By addressing current challenges in data analysis and in bioinformatics software development, this thesis lays the groundwork for future research in bioinformatics and oncology, ultimately aiming to create and implement tools for improved genomic and metagenomic cancer dataset analysis

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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