Integrated mining of feature spaces for bioinformatics domain discovery

One of the major challenges in the field of bioinformatics is the elucidation of protein folding for the functional annotation of proteins. The factors that govern protein folding include the chemical, physical, and environmental conditions of the protein\u27s surroundings, which can be measured and exploited for computational discovery purposes. These conditions enable the protein to transform from a sequence of amino acids to a globular three-dimensional structure. Information concerning the folded state of a protein has significant potential to explain biochemical pathways and their involvement in disorders and diseases. This information impacts the ways in which genetic diseases are characterized and cured and in which designer drugs are created. With the exponential growth of protein databases and the limitations of experimental protein structure determination, sophisticated computational methods have been developed and applied to search for, detect, and compare protein homology. Most computational tools developed for protein structure prediction are primarily based on sequence similarity searches. These approaches have improved the prediction accuracy of high sequence similarity proteins but have failed to perform well with proteins of low sequence similarity. Data mining offers unique algorithmic computational approaches that have been used widely in the development of automatic protein structure classification and prediction. In this dissertation, we present a novel approach for the integration of physico-chemical properties and effective feature extraction techniques for the classification of proteins. Our approaches overcome one of the major obstacles of data mining in protein databases, the encapsulation of different hydrophobicity residue properties into a much reduced feature space that possess high degrees of specificity and sensitivity in protein structure classification. We have developed three unique computational algorithms for coherent feature extraction on selected scale properties of the protein sequence. When plagued by the problem of the unequal cardinality of proteins, our proposed integration scheme effectively handles the varied sizes of proteins and scales well with increasing dimensionality of these sequences. We also detail a two-fold methodology for protein functional annotation. First, we exhibit our success in creating an algorithm that provides a means to integrate multiple physico-chemical properties in the form of a multi-layered abstract feature space, with each layer corresponding to a physico-chemical property. Second, we discuss a wavelet-based segmentation approach that efficiently detects regions of property conservation across all layers of the created feature space. Finally, we present a unique graph-theory based algorithmic framework for the identification of conserved hydrophobic residue interaction patterns using identified scales of hydrophobicity. We report that these discriminatory features are specific to a family of proteins, which consist of conserved hydrophobic residues that are then used for structural classification. We also present our rigorously tested validation schemes, which report significant degrees of accuracy to show that homologous proteins exhibit the conservation of physico-chemical properties along the protein backbone. We conclude our discussion by summarizing our results and contributions and by listing our goals for future research

Scene graph generation: A comprehensive survey

Deep learning techniques have led to remarkable breakthroughs in the field of object detection and have spawned a lot of scene-understanding tasks in recent years. Scene graph has been the focus of research because of its powerful semantic representation and applications to scene understanding. Scene Graph Generation (SGG) refers to the task of automatically mapping an image or a video into a semantic structural scene graph, which requires the correct labeling of detected objects and their relationships. In this paper, a comprehensive survey of recent achievements is provided. This survey attempts to connect and systematize the existing visual relationship detection methods, to summarize, and interpret the mechanisms and the strategies of SGG in a comprehensive way. Deep discussions about current existing problems and future research directions are given at last. This survey will help readers to develop a better understanding of the current researches

A lightweight, graph-theoretic model of class-based similarity to support object-oriented code reuse.

The work presented in this thesis is principally concerned with the development of a method and set of tools designed to support the identification of class-based similarity in collections of object-oriented code. Attention is focused on enhancing the potential for software reuse in situations where a reuse process is either absent or informal, and the characteristics of the organisation are unsuitable, or resources unavailable, to promote and sustain a systematic approach to reuse. The approach builds on the definition of a formal, attributed, relational model that captures the inherent structure of class-based, object-oriented code. Based on code-level analysis, it relies solely on the structural characteristics of the code and the peculiarly object-oriented features of the class as an organising principle: classes, those entities comprising a class, and the intra and inter-class relationships existing between them, are significant factors in defining a two-phase similarity measure as a basis for the comparison process. Established graph-theoretic techniques are adapted and applied via this model to the problem of determining similarity between classes. This thesis illustrates a successful transfer of techniques from the domains of molecular chemistry and computer vision. Both domains provide an existing template for the analysis and comparison of structures as graphs. The inspiration for representing classes as attributed relational graphs, and the application of graph-theoretic techniques and algorithms to their comparison, arose out of a well-founded intuition that a common basis in graph-theory was sufficient to enable a reasonable transfer of these techniques to the problem of determining similarity in object-oriented code. The practical application of this work relates to the identification and indexing of instances of recurring, class-based, common structure present in established and evolving collections of object-oriented code. A classification so generated additionally provides a framework for class-based matching over an existing code-base, both from the perspective of newly introduced classes, and search "templates" provided by those incomplete, iteratively constructed and refined classes associated with current and on-going development. The tools and techniques developed here provide support for enabling and improving shared awareness of reuse opportunity, based on analysing structural similarity in past and ongoing development, tools and techniques that can in turn be seen as part of a process of domain analysis, capable of stimulating the evolution of a systematic reuse ethic

Metrics of Graph-Based Meaning Representations with Applications from Parsing Evaluation to Explainable NLG Evaluation and Semantic Search

"Who does what to whom?" The goal of a graph-based meaning representation (in short: MR) is to represent the meaning of a text in a structured format. With an MR, we can explicate the meaning of a text, describe occurring events and entities, and their semantic relations. Thus, a metric of MRs would measure a distance (or similarity) between MRs. We believe that such a meaning-focused similarity measurement can be useful for several important AI tasks, for instance, testing the capability of systems to produce meaningful output (system evaluation), or when searching for similar texts (information retrieval). Moreover, due to the natural explicitness of MRs, we hypothesize that MR metrics could provide us with valuable explainability of their similarity measurement. Indeed, if texts reside in a space where their meaning has been isolated and structured, we might directly see in which aspects two texts are actually similar (or dissimilar). However, we find that there is not much previous work on MR metrics, and thus we lack fundamental knowledge about them and their potential applications. Therefore, we make first steps to explore MR metrics and MR spaces, focusing on two key goals: 1. Develop novel and generally applicable methods for conducting similarity measurements in the space of MRs; 2. Explore potential applications that can profit from similarity assessments in MR spaces, including, but (by far) not limited to, their "classic" purpose of evaluating the quality of a text-to-MR system against a reference (aka parsing evaluation). We start by analyzing contributions from previous works that have proposed MR metrics for parsing evaluation. Then, we move beyond this restricted setup and start to develop novel and more general MR metrics based on i) insights from our analysis of the previous parsing evaluation metrics and ii) our motivation to extend MR metrics to similarity assessment of natural language texts. To empirically evaluate and assess our generalized MR metrics, and to open the door for future improvements, we propose the first benchmark of MR metrics. With our benchmark, we can study MR metrics through the lens of multiple metric-objectives such as sentence similarity and robustness. Then, we investigate novel applications of MR metrics. First, we explore new ways of applying MR metrics to evaluate systems that produce i) text from MRs (MR-to-text evaluation) and ii) MRs from text (MR parsing). We call our new setting MR projection-based, since we presume that one MR (at least) is unobserved and needs to be approximated. An advantage of such projection-based MR metric methods is that we can ablate a costly human reference. Notably, when visiting the MR-to-text scenario, we touch on a much broader application scenario for MR metrics: explainable MR-grounded evaluation of text generation systems. Moving steadily towards the application of MR metrics to general text similarity, we study MR metrics for measuring the meaning similarity of natural language arguments, which is an important task in argument mining, a new and surging area of natural language processing (NLP). In particular, we show that MRs and MR metrics can support an explainable and unsupervised argument similarity analysis and inform us about the quality of argumentative conclusions. Ultimately, we seek even more generality and are also interested in practical aspects such as efficiency. To this aim, we distill our insights from our hitherto explorations into MR metric spaces into an explainable state-of-the-art machine learning model for semantic search, a task for which we would like to achieve high accuracy and great efficiency. To this aim, we develop a controllable metric distillation approach that can explain how the similarity decisions in the neural text embedding space are modulated through interpretable features, while maintaining all efficiency and accuracy (sometimes improving it) of a high-performance neural semantic search method. This is an important contribution, since it shows i) that we can alleviate the efficiency bottleneck of computationally costly MR graph metrics and, vice versa, ii) that MR metrics can help mitigate a crucial limitation of large "black box" neural methods by eliciting explanations for decisions

A hybrid algorithm for Bayesian network structure learning with application to multi-label learning

We present a novel hybrid algorithm for Bayesian network structure learning, called H2PC. It first reconstructs the skeleton of a Bayesian network and then performs a Bayesian-scoring greedy hill-climbing search to orient the edges. The algorithm is based on divide-and-conquer constraint-based subroutines to learn the local structure around a target variable. We conduct two series of experimental comparisons of H2PC against Max-Min Hill-Climbing (MMHC), which is currently the most powerful state-of-the-art algorithm for Bayesian network structure learning. First, we use eight well-known Bayesian network benchmarks with various data sizes to assess the quality of the learned structure returned by the algorithms. Our extensive experiments show that H2PC outperforms MMHC in terms of goodness of fit to new data and quality of the network structure with respect to the true dependence structure of the data. Second, we investigate H2PC's ability to solve the multi-label learning problem. We provide theoretical results to characterize and identify graphically the so-called minimal label powersets that appear as irreducible factors in the joint distribution under the faithfulness condition. The multi-label learning problem is then decomposed into a series of multi-class classification problems, where each multi-class variable encodes a label powerset. H2PC is shown to compare favorably to MMHC in terms of global classification accuracy over ten multi-label data sets covering different application domains. Overall, our experiments support the conclusions that local structural learning with H2PC in the form of local neighborhood induction is a theoretically well-motivated and empirically effective learning framework that is well suited to multi-label learning. The source code (in R) of H2PC as well as all data sets used for the empirical tests are publicly available.Comment: arXiv admin note: text overlap with arXiv:1101.5184 by other author

Foreground detection by competitive learning for varying input distributions

Copyright Owner. Versión definitiva disponible en el DOI indicado. López-Rubio, E., Molina-Cabello, M. A., Luque-Baena, R. M., & Domínguez, E. (2018). Foreground detection by competitive learning for varying input distributions. International journal of neural systems, 28(05), 1750056.One of the most important challenges in computer vision applications is the background modeling, especially when the background is dynamic and the input distribution might not be stationary, i.e. the distribution of the input data could change with time (e.g. changing illuminations, waving trees, water, etc.). In this work, an unsupervised learning neural network is proposed which is able to cope with progressive changes in the input distribution. It is based on a dual learning mechanism which manages the changes of the input distribution separately from the cluster detection. The proposal is adequate for scenes where the background varies slowly. The performance of the method is tested against several state-of-the-art foreground detectors both quantitatively and qualitatively, with favorable results

Graph-Based Approaches to Protein StructureComparison - From Local to Global Similarity

The comparative analysis of protein structure data is a central aspect of structural bioinformatics. Drawing upon structural information allows the inference of function for unknown proteins even in cases where no apparent homology can be found on the sequence level. Regarding the function of an enzyme, the overall fold topology might less important than the specific structural conformation of the catalytic site or the surface region of a protein, where the interaction with other molecules, such as binding partners, substrates and ligands occurs. Thus, a comparison of these regions is especially interesting for functional inference, since structural constraints imposed by the demands of the catalyzed biochemical function make them more likely to exhibit structural similarity. Moreover, the comparative analysis of protein binding sites is of special interest in pharmaceutical chemistry, in order to predict cross-reactivities and gain a deeper understanding of the catalysis mechanism. From an algorithmic point of view, the comparison of structured data, or, more generally, complex objects, can be attempted based on different methodological principles. Global methods aim at comparing structures as a whole, while local methods transfer the problem to multiple comparisons of local substructures. In the context of protein structure analysis, it is not a priori clear, which strategy is more suitable. In this thesis, several conceptually different algorithmic approaches have been developed, based on local, global and semi-global strategies, for the task of comparing protein structure data, more specifically protein binding pockets. The use of graphs for the modeling of protein structure data has a long standing tradition in structural bioinformatics. Recently, graphs have been used to model the geometric constraints of protein binding sites. The algorithms developed in this thesis are based on this modeling concept, hence, from a computer scientist's point of view, they can also be regarded as global, local and semi-global approaches to graph comparison. The developed algorithms were mainly designed on the premise to allow for a more approximate comparison of protein binding sites, in order to account for the molecular flexibility of the protein structures. A main motivation was to allow for the detection of more remote similarities, which are not apparent by using more rigid methods. Subsequently, the developed approaches were applied to different problems typically encountered in the field of structural bioinformatics in order to assess and compare their performance and suitability for different problems. Each of the approaches developed during this work was capable of improving upon the performance of existing methods in the field. Another major aspect in the experiments was the question, which methodological concept, local, global or a combination of both, offers the most benefits for the specific task of protein binding site comparison, a question that is addressed throughout this thesis

Augmenting Wiring Diagrams of Neural Circuits with Activity in Larval Drosophila

Neural circuit models explain an animal's behavior as evoked activity of different circuit elements of its nervous system. Synaptic wiring diagrams mapped from structural imaging of nervous systems guide modeling of neural circuits on the basis of connectivity. However, connectivity alone may not sufficiently constrain the set of plausible circuit hypotheses for empirical study. Combining structural imaging of synaptic connectivity with functional information from activity imaging can further constrain these hypotheses to create unequivocal neural circuit models. This thesis develops computational methods and tools to cross-reference structural and activity imaging of explant larval Drosophila central nervous systems at cellular resolution. Augmenting synaptic wiring diagrams with activity maps via these methods relates circuit structure and function at the neuronal level on a per-behavior basis. Neuronal activity of larval central nervous systems expressing pan-neuronal calcium indicators is imaged in a light sheet microscope, which are then structurally imaged with high throughput electron microscopy. Methods and tools are provided for the assembly of these image volumes, spatial registration between imaging modalities, automated detection of relevant tissue and cellular structures in each, extraction of activity time series, and morphological identification of neurons in structural imaging using reference wiring diagrams mapped from other larvae. Using these methods, existing wiring diagrams mapped from a reference first instar larva were identified with neurons in a larva augmented with activity information for a neural circuit involved in peristaltic motor control. This demonstrates the feasibility of the contributed methods to associate the wiring diagrams of arbitrary circuits of interest with activity timeseries across multiple individuals, behaviors, and behavioral bouts. To demonstrate capability to augment wiring diagrams with information besides activity, these methods are also applied to multiple larvae each expressing specific neurotransmitter labels rather than calcium indicators in the light sheet microscopy. This work scaffolds future modeling of circuits underlying behavior that can only be mechanistically understood in the context of multi-modal observation of synaptic connectivity, functional activity and molecular markers. The methods developed also enable comparative connectomics between multiple individuals, which is necessary to study inter-individual variability in circuits and to observe experimental intervention in the development, structure, and function of neural circuits.Howard Hughes Medical Institute Janelia Research Campu

Unifying Large Language Models and Knowledge Graphs: A Roadmap

Large language models (LLMs), such as ChatGPT and GPT4, are making new waves in the field of natural language processing and artificial intelligence, due to their emergent ability and generalizability. However, LLMs are black-box models, which often fall short of capturing and accessing factual knowledge. In contrast, Knowledge Graphs (KGs), Wikipedia and Huapu for example, are structured knowledge models that explicitly store rich factual knowledge. KGs can enhance LLMs by providing external knowledge for inference and interpretability. Meanwhile, KGs are difficult to construct and evolving by nature, which challenges the existing methods in KGs to generate new facts and represent unseen knowledge. Therefore, it is complementary to unify LLMs and KGs together and simultaneously leverage their advantages. In this article, we present a forward-looking roadmap for the unification of LLMs and KGs. Our roadmap consists of three general frameworks, namely, 1) KG-enhanced LLMs, which incorporate KGs during the pre-training and inference phases of LLMs, or for the purpose of enhancing understanding of the knowledge learned by LLMs; 2) LLM-augmented KGs, that leverage LLMs for different KG tasks such as embedding, completion, construction, graph-to-text generation, and question answering; and 3) Synergized LLMs + KGs, in which LLMs and KGs play equal roles and work in a mutually beneficial way to enhance both LLMs and KGs for bidirectional reasoning driven by both data and knowledge. We review and summarize existing efforts within these three frameworks in our roadmap and pinpoint their future research directions.Comment: 29 pages, 25 figure