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

Biomedical applications of belief networks

Biomedicine is an area in which computers have long been expected to play a significant role. Although many of the early claims have proved unrealistic, computers are gradually becoming accepted in the biomedical, clinical and research environment. Within these application areas, expert systems appear to have met with the most resistance, especially when applied to image interpretation.In order to improve the acceptance of computerised decision support systems it is necessary to provide the information needed to make rational judgements concerning the inferences the system has made. This entails an explanation of what inferences were made, how the inferences were made and how the results of the inference are to be interpreted. Furthermore there must be a consistent approach to the combining of information from low level computational processes through to high level expert analyses.nformation from low level computational processes through to high level expert analyses. Until recently ad hoc formalisms were seen as the only tractable approach to reasoning under uncertainty. A review of some of these formalisms suggests that they are less than ideal for the purposes of decision making. Belief networks provide a tractable way of utilising probability theory as an inference formalism by combining the theoretical consistency of probability for inference and decision making, with the ability to use the knowledge of domain experts.nowledge of domain experts. The potential of belief networks in biomedical applications has already been recog¬ nised and there has been substantial research into the use of belief networks for medical diagnosis and methods for handling large, interconnected networks. In this thesis the use of belief networks is extended to include detailed image model matching to show how, in principle, feature measurement can be undertaken in a fully probabilistic way. The belief networks employed are usually cyclic and have strong influences between adjacent nodes, so new techniques for probabilistic updating based on a model of the matching process have been developed.An object-orientated inference shell called FLAPNet has been implemented and used to apply the belief network formalism to two application domains. The first application is model-based matching in fetal ultrasound images. The imaging modality and biological variation in the subject make model matching a highly uncertain process. A dynamic, deformable model, similar to active contour models, is used. A belief network combines constraints derived from local evidence in the image, with global constraints derived from trained models, to control the iterative refinement of an initial model cue.In the second application a belief network is used for the incremental aggregation of evidence occurring during the classification of objects on a cervical smear slide as part of an automated pre-screening system. A belief network provides both an explicit domain model and a mechanism for the incremental aggregation of evidence, two attributes important in pre-screening systems.Overall it is argued that belief networks combine the necessary quantitative features required of a decision support system with desirable qualitative features that will lead to improved acceptability of expert systems in the biomedical domain

Executable cancer models: successes and challenges

Making decisions on how best to treat cancer patients requires the integration of different data sets, including genomic profiles, tumour histopathology, radiological images, proteomic analysis and more. This wealth of biological information calls for novel strategies to integrate such information in a meaningful, predictive and experimentally verifiable way. In this Perspective we explain how executable computational models meet this need. Such models provide a means for comprehensive data integration, can be experimentally validated, are readily interpreted both biologically and clinically, and have the potential to predict effective therapies for different cancer types and subtypes. We explain what executable models are and how they can be used to represent the dynamic biological behaviours inherent in cancer, and demonstrate how such models, when coupled with automated reasoning, facilitate our understanding of the mechanisms by which oncogenic signalling pathways regulate tumours. We explore how executable models have impacted the field of cancer research and argue that extending them to represent a tumour in a specific patient (that is, an avatar) will pave the way for improved personalized treatments and precision medicine. Finally, we highlight some of the ongoing challenges in developing executable models and stress that effective cross-disciplinary efforts are key to forward progress in the field

Memory effects in biochemical networks as the natural counterpart of extrinsic noise

We show that in the generic situation where a biological network, e.g. a protein interaction network, is in fact a subnetwork embedded in a larger "bulk" network, the presence of the bulk causes not just extrinsic noise but also memory effects. This means that the dynamics of the subnetwork will depend not only on its present state, but also its past. We use projection techniques to get explicit expressions for the memory functions that encode such memory effects, for generic protein interaction networks involving binary and unary reactions such as complex formation and phosphorylation, respectively. Remarkably, in the limit of low intrinsic copy-number noise such expressions can be obtained even for nonlinear dependences on the past. We illustrate the method with examples from a protein interaction network around epidermal growth factor receptor (EGFR), which is relevant to cancer signalling. These examples demonstrate that inclusion of memory terms is not only important conceptually but also leads to substantially higher quantitative accuracy in the predicted subnetwork dynamics

Categorical Ontology of Complex Systems, Meta-Systems and Theory of Levels: The Emergence of Life, Human Consciousness and Society

Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quantum states emerging from complex quantum dynamics of interacting networks of biomolecules, such as proteins and nucleic acids that are now collectively defined as quantum interactomics. On the other hand, the time dependent evolution over several generations of cancer cells --that are generally known to undergo frequent and extensive genetic mutations and, indeed, suffer genomic transformations at the chromosome level (such as extensive chromosomal aberrations found in many colon cancers)-- cannot be correctly represented in the ‘standard’ terms of quantum automaton modules, as the normal somatic cells can. This significant difference at the cancer cell genomic level is therefore reflected in major changes in cancer cell interactomics often from one cancer cell ‘cycle’ to the next, and thus it requires substantial changes in the modeling strategies, mathematical tools and experimental designs aimed at understanding cancer mechanisms. Novel solutions to this important problem in carcinogenesis are proposed and experimental validation procedures are suggested. From a medical research and clinical standpoint, this approach has important consequences for addressing and preventing the development of cancer resistance to medical therapy in ongoing clinical trials involving stage III cancer patients, as well as improving the designs of future clinical trials for cancer treatments.\ud \ud \ud KEYWORDS: Emergence of Life and Human Consciousness;\ud Proteomics; Artificial Intelligence; Complex Systems Dynamics; Quantum Automata models and Quantum Interactomics; quantum-weave dynamic patterns underlying human consciousness; specific molecular processes underlying extensive memory, learning, anticipation mechanisms and human consciousness; emergence of human consciousness during the early brain development in children; Cancer cell ‘cycling’; interacting networks of proteins and nucleic acids; genetic mutations and chromosomal aberrations in cancers, such as colon cancer; development of cancer resistance to therapy; ongoing clinical trials involving stage III cancer patients’ possible improvements of the designs for future clinical trials and cancer treatments. \ud \u

The Design of Interactive Visualizations and Analytics for Public Health Data

Public health data plays a critical role in ensuring the health of the populace. Professionals use data as they engage in efforts to improve and protect the health of communities. For the public, data influences their ability to make health-related decisions. Health literacy, which is the ability of an individual to access, understand, and apply health data, is a key determinant of health. At present, people seeking to use public health data are confronted with a myriad of challenges some of which relate to the nature and structure of the data. Interactive visualizations are a category of computational tools that can support individuals as they seek to use public health data. With interactive visualizations, individuals can access underlying data, change how data is represented, manipulate various visual elements, and in certain tools control and perform analytic tasks. That being said, currently, in public health, simple visualizations, which fail to effectively support the exploration of large sets of data, are predominantly used. The goal of this dissertation is to demonstrate the benefit of sophisticated interactive visualizations and analytics. As improperly designed visualizations can negatively impact users’ discourse with data, there is a need for frameworks to help designers think systematically about design issues. Furthermore, there is a need to demonstrate how such frameworks can be utilized. This dissertation includes a process by which designers can create health visualizations. Using this process, five novel visualizations were designed to facilitate making sense of public health data. Three studies were conducted with the visualizations. The first study explores how computational models can be used to make sense of the discourse of health on a social media platform. The second study investigates the use of instructional materials to improve visualization literacy. Visualization literacy is important because even when visualizations are designed properly, there still exists a gap between how a tool works and users’ perceptions of how the tool should work. The last study examines the efficacy of visualizations to improve health literacy. Overall then, this dissertation provides designers with a deeper understanding of how to systematically design health visualizations

Critical Thinking Skills Profile of High School Students In Learning Science-Physics

This study aims to describe Critical Thinking Skills high school students in the city of Makassar. To achieve this goal, the researchers conducted an analysis of student test results of 200 people scattered in six schools in the city of Makassar. The results of the quantitative descriptive analysis of the data found that the average value of students doing the interpretation, analysis, and inference in a row by 1.53, 1.15, and 1.52. This value is still very low when compared with the maximum value that may be obtained by students, that is equal to 10.00. This shows that the critical thinking skills of high school students are still very low. One fact Competency Standards science subjects-Physics is demonstrating the ability to think logically, critically, and creatively with the guidance of teachers and demonstrate the ability to solve simple problems in daily life. In fact, according to Michael Scriven stated that the main task of education is to train students and or students to think critically because of the demands of work in the global economy, the survival of a democratic and personal decisions and decisions in an increasingly complex society needs people who can think well and make judgments good. Therefore, the need for teachers in the learning device scenario such as: driving question or problem, authentic Investigation: Science Processes

Models for prediction, explanation and control: recursive bayesian networks

The Recursive Bayesian Net (RBN) formalism was originally developed for modelling nested causal relationships. In this paper we argue that the formalism can also be applied to modelling the hierarchical structure of mechanisms. The resulting network contains quantitative information about probabilities, as well as qualitative information about mechanistic structure and causal relations. Since information about probabilities, mechanisms and causal relations is vital for prediction, explanation and control respectively, an RBN can be applied to all these tasks. We show in particular how a simple two-level RBN can be used to model a mechanism in cancer science. The higher level of our model contains variables at the clinical level, while the lower level maps the structure of the cell's mechanism for apoptosis