Protein Bioinformatics Infrastructure for the Integration and Analysis of Multiple High-Throughput “omics” Data

High-throughput “omics” technologies bring new opportunities for biological and biomedical researchers to ask complex questions and gain new scientific insights. However, the voluminous, complex, and context-dependent data being maintained in heterogeneous and distributed environments plus the lack of well-defined data standard and standardized nomenclature imposes a major challenge which requires advanced computational methods and bioinformatics infrastructures for integration, mining, visualization, and comparative analysis to facilitate data-driven hypothesis generation and biological knowledge discovery. In this paper, we present the challenges in high-throughput “omics” data integration and analysis, introduce a protein-centric approach for systems integration of large and heterogeneous high-throughput “omics” data including microarray, mass spectrometry, protein sequence, protein structure, and protein interaction data, and use scientific case study to illustrate how one can use varied “omics” data from different laboratories to make useful connections that could lead to new biological knowledge

The Retrosplenial Cortex: Intrinsic Connectivity and Connections with the (Para)Hippocampal Region in the Rat. An Interactive Connectome

A connectome is an indispensable tool for brain researchers, since it quickly provides comprehensive knowledge of the brain's anatomical connections. Such knowledge lies at the basis of understanding network functions. Our first comprehensive and interactive account of brain connections comprised the rat hippocampal–parahippocampal network. We have now added all anatomical connections with the retrosplenial cortex (RSC) as well as the intrinsic connections of this region, because of the interesting functional overlap between these brain regions. The RSC is involved in a variety of cognitive tasks including memory, navigation, and prospective thinking, yet the exact role of the RSC and the functional differences between its subdivisions remain elusive. The connectome presented here may help to define this role by providing an unprecedented interactive and searchable overview of all connections within and between the rat RSC, parahippocampal region and hippocampal formation

‘The uses of ethnography in the science of cultural evolution’. Commentary on Mesoudi, A., Whiten, A. and K. Laland ‘Toward a unified science of cultural evolution’

There is considerable scope for developing a more explicit role for ethnography within the research program proposed in the article. Ethnographic studies of cultural micro-evolution would complement experimental approaches by providing insights into the “natural” settings in which cultural behaviours occur. Ethnography can also contribute to the study of cultural macro-evolution by shedding light on the conditions that generate and maintain cultural lineages

Placing Birds On A Dynamic Evolutionary Map: Using Digital Tools To Update The Evolutionary Metaphor Of The Tree Of Life

This dissertation describes and presents a new type of interactive visualization for communicating about evolutionary biology, the dynamic evolutionary map. This web-based tool utilizes a novel map-based metaphor to visualize evolution, rather than the traditional tree of life. The dissertation begins with an analysis of the conceptual affordances of the traditional tree of life as the dominant metaphor for evolution. Next, theories from digital media, visualization, and cognitive science research are synthesized to support the assertion that digital media tools can extend the types of visual metaphors we use in science communication in order to overcome conceptual limitations of traditional metaphors. These theories are then applied to a specific problem of science communication, resulting in the dynamic evolutionary map. Metaphor is a crucial part of scientific communication, and metaphor-based scientific visualizations, models, and analogies play a profound role in shaping our ideas about the world around us. Users of the dynamic evolutionary map interact with evolution in two ways: by observing the diversification of bird orders over time and by examining the evidence for avian evolution at several places in evolutionary history. By combining these two types of interaction with a non-traditional map metaphor, evolution is framed in a novel way that supplements traditional metaphors for communicating about evolution. This reframing in turn suggests new conceptual affordances to users who are learning about evolution. Empirical testing of the dynamic evolutionary map by biology novices suggests that this approach is successful in communicating evolution differently than in existing tree-based visualization methods. Results of evaluation of the map by biology experts suggest possibilities for future enhancement and testing of this visualization that would help refine these successes. This dissertation represents an important step forward in the synthesis of scientific, design, and metaphor theory, as applied to a specific problem of science communication. The dynamic evolutionary map demonstrates that these theories can be used to guide the construction of a visualization for communicating a scientific concept in a way that is both novel and grounded in theory. There are several potential applications in the fields of informal science education, formal education, and evolutionary biology for the visualization created in this dissertation. Moreover, the approach suggested in this dissertation can potentially be extended into other areas of science and science communication. By placing birds onto the dynamic evolutionary map, this dissertation points to a way forward for visualizing science communication in the futur

A Theory of Conceptual Advance: Explaining Conceptual Change in Evolutionary, Molecular, and Evolutionary Developmental Biology

The theory of concepts advanced in the dissertation aims at accounting for a) how a concept makes successful practice possible, and b) how a scientific concept can be subject to rational change in the course of history. Traditional accounts in the philosophy of science have usually studied concepts in terms only of their reference; their concern is to establish a stability of reference in order to address the incommensurability problem. My discussion, in contrast, suggests that each scientific concept consists of three components of content: 1) reference, 2) inferential role, and 3) the epistemic goal pursued with the concept's use. I argue that in the course of history a concept can change in any of these three components, and that change in one component—including change of reference—can be accounted for as being rational relative to other components, in particular a concept's epistemic goal.This semantic framework is applied to two cases from the history of biology: the homology concept as used in 19th and 20th century biology, and the gene concept as used in different parts of the 20th century. The homology case study argues that the advent of Darwinian evolutionary theory, despite introducing a new definition of homology, did not bring about a new homology concept (distinct from the pre-Darwinian concept) in the 19th century. Nowadays, however, distinct homology concepts are used in systematics/evolutionary biology, in evolutionary developmental biology, and in molecular biology. The emergence of these different homology concepts is explained as occurring in a rational fashion. The gene case study argues that conceptual progress occurred with the transition from the classical to the molecular gene concept, despite a change in reference. In the last two decades, change occurred internal to the molecular gene concept, so that nowadays this concept's usage and reference varies from context to context. I argue that this situation emerged rationally and that the current variation in usage and reference is conducive to biological practice.The dissertation uses ideas and methodological tools from the philosophy of mind and language, the philosophy of science, the history of science, and the psychology of concepts

Computational Approaches to Drug Profiling and Drug-Protein Interactions

Despite substantial increases in R&D spending within the pharmaceutical industry, denovo drug design has become a time-consuming endeavour. High attrition rates led to a long period of stagnation in drug approvals. Due to the extreme costs associated with introducing a drug to the market, locating and understanding the reasons for clinical failure is key to future productivity. As part of this PhD, three main contributions were made in this respect. First, the web platform, LigNFam enables users to interactively explore similarity relationships between ‘drug like’ molecules and the proteins they bind. Secondly, two deep-learning-based binding site comparison tools were developed, competing with the state-of-the-art over benchmark datasets. The models have the ability to predict offtarget interactions and potential candidates for target-based drug repurposing. Finally, the open-source ScaffoldGraph software was presented for the analysis of hierarchical scaffold relationships and has already been used in multiple projects, including integration into a virtual screening pipeline to increase the tractability of ultra-large screening experiments. Together, and with existing tools, the contributions made will aid in the understanding of drug-protein relationships, particularly in the fields of off-target prediction and drug repurposing, helping to design better drugs faster