Interactive knowledge discovery and data mining on genomic expression data with numeric formal concept analysis

Background: Gene Expression Data (GED) analysis poses a great challenge to the scientific community that can be framed into the Knowledge Discovery in Databases (KDD) and Data Mining (DM) paradigm. Biclustering has emerged as the machine learning method of choice to solve this task, but its unsupervised nature makes result assessment problematic. This is often addressed by means of Gene Set Enrichment Analysis (GSEA). Results: We put forward a framework in which GED analysis is understood as an Exploratory Data Analysis (EDA) process where we provide support for continuous human interaction with data aiming at improving the step of hypothesis abduction and assessment. We focus on the adaptation to human cognition of data interpretation and visualization of the output of EDA. First, we give a proper theoretical background to bi-clustering using Lattice Theory and provide a set of analysis tools revolving around K-Formal Concept Analysis (K-FCA), a lattice-theoretic unsupervised learning technique for real-valued matrices. By using different kinds of cost structures to quantify expression we obtain different sequences of hierarchical bi-clusterings for gene under- and over-expression using thresholds. Consequently, we provide a method with interleaved analysis steps and visualization devices so that the sequences of lattices for a particular experiment summarize the researcher’s vision of the data. This also allows us to define measures of persistence and robustness of biclusters to assess them. Second, the resulting biclusters are used to index external omics databases—for instance, Gene Ontology (GO)—thus offering a new way of accessing publicly available resources. This provides different flavors of gene set enrichment against which to assess the biclusters, by obtaining their p-values according to the terminology of those resources. We illustrate the exploration procedure on a real data example confirming results previously published. Conclusions: The GED analysis problem gets transformed into the exploration of a sequence of lattices enabling the visualization of the hierarchical structure of the biclusters with a certain degree of granularity. The ability of FCA-based bi-clustering methods to index external databases such as GO allows us to obtain a quality measure of the biclusters, to observe the evolution of a gene throughout the different biclusters it appears in, to look for relevant biclusters—by observing their genes and what their persistence is—to infer, for instance, hypotheses on their function

Integration of Data Mining into Scientific Data Analysis Processes

In recent years, using advanced semi-interactive data analysis algorithms such as those from the field of data mining gained more and more importance in life science in general and in particular in bioinformatics, genetics, medicine and biodiversity. Today, there is a trend away from collecting and evaluating data in the context of a specific problem or study only towards extensively collecting data from different sources in repositories which is potentially useful for subsequent analysis, e.g. in the Gene Expression Omnibus (GEO) repository of high throughput gene expression data. At the time the data are collected, it is analysed in a specific context which influences the experimental design. However, the type of analyses that the data will be used for after they have been deposited is not known. Content and data format are focused only to the first experiment, but not to the future re-use. Thus, complex process chains are needed for the analysis of the data. Such process chains need to be supported by the environments that are used to setup analysis solutions. Building specialized software for each individual problem is not a solution, as this effort can only be carried out for huge projects running for several years. Hence, data mining functionality was developed to toolkits, which provide data mining functionality in form of a collection of different components. Depending on the different research questions of the users, the solutions consist of distinct compositions of these components. Today, existing solutions for data mining processes comprise different components that represent different steps in the analysis process. There exist graphical or script-based toolkits for combining such components. The data mining tools, which can serve as components in analysis processes, are based on single computer environments, local data sources and single users. However, analysis scenarios in medical- and bioinformatics have to deal with multi computer environments, distributed data sources and multiple users that have to cooperate. Users need support for integrating data mining into analysis processes in the context of such scenarios, which lacks today. Typically, analysts working with single computer environments face the problem of large data volumes since tools do not address scalability and access to distributed data sources. Distributed environments such as grid environments provide scalability and access to distributed data sources, but the integration of existing components into such environments is complex. In addition, new components often cannot be directly developed in distributed environments. Moreover, in scenarios involving multiple computers, multiple distributed data sources and multiple users, the reuse of components, scripts and analysis processes becomes more important as more steps and configuration are necessary and thus much bigger efforts are needed to develop and set-up a solution. In this thesis we will introduce an approach for supporting interactive and distributed data mining for multiple users based on infrastructure principles that allow building on data mining components and processes that are already available instead of designing of a completely new infrastructure, so that users can keep working with their well-known tools. In order to achieve the integration of data mining into scientific data analysis processes, this thesis proposes an stepwise approach of supporting the user in the development of analysis solutions that include data mining. We see our major contributions as the following: first, we propose an approach to integrate data mining components being developed for a single processor environment into grid environments. By this, we support users in reusing standard data mining components with small effort. The approach is based on a metadata schema definition which is used to grid-enable existing data mining components. Second, we describe an approach for interactively developing data mining scripts in grid environments. The approach efficiently supports users when it is necessary to enhance available components, to develop new data mining components, and to compose these components. Third, building on that, an approach for facilitating the reuse of existing data mining processes based on process patterns is presented. It supports users in scenarios that cover different steps of the data mining process including several components or scripts. The data mining process patterns support the description of data mining processes at different levels of abstraction between the CRISP model as most general and executable workflows as most concrete representation

Supporting scientific knowledge discovery with extended, generalized Formal Concept Analysis

In this paper we fuse together the Landscapes of Knowledge of Wille's and Exploratory Data Analysis by leveraging Formal Concept Analysis (FCA) to support data-induced scientific enquiry and discovery. We use extended FCA first by allowing K-valued entries in the incidence to accommodate other, non-binary types of data, and second with different modes of creating formal concepts to accommodate diverse conceptualizing phenomena. With these extensions we demonstrate the versatility of the Landscapes of Knowledge metaphor to help in creating new scientific and engineering knowledge by providing several successful use cases of our techniques that support scientific hypothesis-making and discovery in a range of domains: semiring theory, perceptual studies, natural language semantics, and gene expression data analysis. While doing so, we also capture the affordances that justify the use of FCA and its extensions in scientific discovery.FJVA and AP were partially supported by EUFP7 project LiMo- SINe (contract288024) for this research. CPM was partially supported by the Spanish Ministry of Economics and Competitiveness projects TEC2014-61729-EXP and TEC2014-53390-P

Using machine learning to support better and intelligent visualisation for genomic data

Massive amounts of genomic data are created for the advent of Next Generation Sequencing technologies. Great technological advances in methods of characterising the human diseases, including genetic and environmental factors, make it a great opportunity to understand the diseases and to find new diagnoses and treatments. Translating medical data becomes more and more rich and challenging. Visualisation can greatly aid the processing and integration of complex data. Genomic data visual analytics is rapidly evolving alongside with advances in high-throughput technologies such as Artificial Intelligence (AI), and Virtual Reality (VR). Personalised medicine requires new genomic visualisation tools, which can efficiently extract knowledge from the genomic data effectively and speed up expert decisions about the best treatment of an individual patient’s needs. However, meaningful visual analysis of such large genomic data remains a serious challenge. Visualising these complex genomic data requires not only simply plotting of data but should also lead to better decisions. Machine learning has the ability to make prediction and aid in decision-making. Machine learning and visualisation are both effective ways to deal with big data, but they focus on different purposes. Machine learning applies statistical learning techniques to automatically identify patterns in data to make highly accurate prediction, while visualisation can leverage the human perceptual system to interpret and uncover hidden patterns in big data. Clinicians, experts and researchers intend to use both visualisation and machine learning to analyse their complex genomic data, but it is a serious challenge for them to understand and trust machine learning models in the serious medical industry. The main goal of this thesis is to study the feasibility of intelligent and interactive visualisation which combined with machine learning algorithms for medical data analysis. A prototype has also been developed to illustrate the concept that visualising genomics data from childhood cancers in meaningful and dynamic ways could lead to better decisions. Machine learning algorithms are used and illustrated during visualising the cancer genomic data in order to provide highly accurate predictions. This research could open a new and exciting path to discovery for disease diagnostics and therapies

BioBridge: Bringing Data Exploration to Biologists

Since the completion of the Human Genome Project in 2003, biologists have become exceptionally good at producing data. Indeed, biological data has experienced a sustained exponential growth rate, putting effective and thorough analysis beyond the reach of many biologists. This thesis presents BioBridge, an interactive visualization tool developed to bring intuitive data exploration to biologists. BioBridge is designed to work on omics style tabular data in general and thus has broad applicability. This work describes the design and evaluation of BioBridge\u27s Entity View primary visualization as well the accompanying user interface. The Entity View visualization arranges glyphs representing biological entities (e.g. genes, proteins, metabolites) along with related text mining results to provide biological context. Throughout development the goal has been to maximize accessibility and usability for biologists who are not computationally inclined. Evaluations were done with three informal case studies, one of a metabolome dataset and two of microarray datasets. BioBridge is a proof of concept that there is an underexploited niche in the data analysis ecosystem for tools that prioritize accessibility and usability. The use case studies, while anecdotal, are very encouraging. These studies indicate that BioBridge is well suited for the task of data exploration. With further development, BioBridge could become more flexible and usable as additional use case datasets are explored and more feedback is gathered

Iterative Visual Analytics and its Applications in Bioinformatics

Indiana University-Purdue University Indianapolis (IUPUI)You, Qian. Ph.D., Purdue University, December, 2010. Iterative Visual Analytics and its Applications in Bioinformatics. Major Professors: Shiaofen Fang and Luo Si. Visual Analytics is a new and developing field that addresses the challenges of knowledge discoveries from the massive amount of available data. It facilitates humans‘ reasoning capabilities with interactive visual interfaces for exploratory data analysis tasks, where automatic data mining methods fall short due to the lack of the pre-defined objective functions. Analyzing the large volume of data sets for biological discoveries raises similar challenges. The domain knowledge of biologists and bioinformaticians is critical in the hypothesis-driven discovery tasks. Yet developing visual analytics frameworks for bioinformatic applications is still in its infancy. In this dissertation, we propose a general visual analytics framework – Iterative Visual Analytics (IVA) – to address some of the challenges in the current research. The framework consists of three progressive steps to explore data sets with the increased complexity: Terrain Surface Multi-dimensional Data Visualization, a new multi-dimensional technique that highlights the global patterns from the profile of a large scale network. It can lead users‘ attention to characteristic regions for discovering otherwise hidden knowledge; Correlative Multi-level Terrain Surface Visualization, a new visual platform that provides the overview and boosts the major signals of the numeric correlations among nodes in interconnected networks of different contexts. It enables users to gain critical insights and perform data analytical tasks in the context of multiple correlated networks; and the Iterative Visual Refinement Model, an innovative process that treats users‘ perceptions as the objective functions, and guides the users to form the optimal hypothesis by improving the desired visual patterns. It is a formalized model for interactive explorations to converge to optimal solutions. We also showcase our approach with bio-molecular data sets and demonstrate its effectiveness in several biomarker discovery applications

Biomedical data retrieval utilizing textual data in a gene expression database by Richard Lu, MD.

Thesis (S.M.)--Harvard-MIT Division of Health Sciences and Technology, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 68-74).Background: The commoditization of high-throughput gene expression sequencing and microarrays has led to a proliferation in both the amount of genomic and clinical data that is available. Descriptive textual information deposited with gene expression data in the Gene Expression Omnibus (GEO) is an underutilized resource because the textual information is unstructured and difficult to query. Rendering this information in a structured format utilizing standard medical terms would facilitate better searching and data reuse. Such a procedure would significantly increase the clinical utility of biomedical data repositories. Methods: The thesis is divided into two sections. The first section compares how well four medical terminologies were able to represent textual information deposited in GEO. The second section implements free-text search and faceted search and evaluates how well they are able to answer clinical queries with varying levels of complexity. Part I: 120 samples were randomly extracted from samples deposited in the GEO database from six clinical domains-breast cancer, colon cancer, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes mellitus (IDDM), and asthma. These samples were previously annotated manually and structured textual information was obtained in a tag:value format. Data was mapped to four different controlled terminologies: NCI Thesaurus, MeSH, SNOMED-CT, and ICD- 10. The samples were assigned a score on a three-point scale that was based on how well the terminology was able to represent descriptive textual information. Part II: Faceted and free-text search tools were implemented, with 300 GEO samples included for querying. Eight natural language search questions were selected randomly from scientific journals. Academic researchers were recruited and asked to use the faceted and free-text search tools to locate samples matching the question criteria. Precision, recall, F-score, and search time were compared and analyzed for both free-text and faceted search. Results: The results show that the NCI Thesaurus consistently ranked as the most comprehensive terminology across all domains while ICD-10 consistently ranked as the least comprehensive. Using NCI Thesaurus to augment the faceted search tool, each researcher was able to reach 100% precision and recall (F-score 1.0) for each of the eight search questions. Using free-text search, test users averaged 22.8% precision, 60.7% recall, and an F-score of 0.282. The mean search time per question using faceted search and free-text search were 116.7 seconds, and 138.4 seconds, respectively. The difference between search time was not statistically significant (p=0. 734). However, paired t-test analysis showed a statistically signficant difference between the two search strategies with respect to precision (p=O.001), recall (p=O.042), and F-score (p<0. 001). Conclusion: This work demonstrates that biomedical terms included in a gene expression database can be adequately expressed using the NCI Thesaurus. It also shows that faceted searching using a controlled terminology is superior to conventional free-text searching when answering queries of varying levels of complexity.S.M

First Elements on Knowledge Discovery guided by Domain Knowledge (KDDK)

International audienceIn this paper, we present research trends carried out in the Orpailleur team at Loria, showing how knowledge discovery and knowledge processing may be combined. The knowledge discovery in databases process (KDD) consists in processing a huge volume of data for extracting significant and reusable knowledge units. From a knowledge representation perspective, the KDD process may take advantage of domain knowledge embedded in ontologies relative to the domain of data, leading to the notion of ''knowledge discovery guided by domain knowledge'' or KDDK. The KDDK process is based on the classification process (and its multiple forms), e.g. for modeling, representing, reasoning, and discovering. Some applications are detailed, showing how KDDK can be instantiated in an application domain. Finally, an architecture of an integrated KDDK system is proposed and discussed