Jörg Wicker

Collaborative development of predictive toxicology applications

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals.The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation.Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure-activity relationship modelling of REACH-relevant endpoints: ToxPredict which predicts and reports on toxicities for endpoints for an input chemical structure, and ToxCreate which builds and validates a predictive toxicity model based on an input toxicology dataset. Because of the extensible nature of the standardised Framework design, barriers of interoperability between applications and content are removed, as the user may combine data, models and validation from multiple sources in a dependable and time-effective way.

Cinema audiences reproducibly vary the chemical composition of air during films, by broadcasting scene specific emissions on breath.

Human beings continuously emit chemicals into the air by breath and through the skin. In order to determine whether these emissions vary predictably in response to audiovisual stimuli, we have continuously monitored carbon dioxide and over one hundred volatile organic compounds in a cinema. It was found that many airborne chemicals in cinema air varied distinctively and reproducibly with time for a particular film, even in different screenings to different audiences. Application of scene labels and advanced data mining methods revealed that specific film events, namely “suspense” or “comedy” caused audiences to change their emission of specific chemicals. These event-type synchronous, broadcasted human chemosignals open the possibility for objective and non-invasive assessment of a human group response to stimuli by continuous measurement of chemicals in air. Such methods can be applied to research fields such as psychology and biology, and be valuable to industries such as film making and advertising.

Inductive databases in the relational model: the data as the bridge

We present a new and comprehensive approach to inductive databases in the relational model. The main contribution is a new inductive query language extending SQL, with the goal of supporting the whole knowledge discovery process, from pre-processing via data mining to post-processing. A prototype system supporting the query language was developed in the SINDBAD (structured inductive database development) project. Setting aside models and focusing on distance-based and instance-based methods, closure can easily be achieved. An example scenario from the area of gene expression data analysis demonstrates the power and simplicity of the concept. We hope that this preliminary work will help to bring the fundamental issues, such as the integration of various pattern domains and data mining techniques, to the attention of the inductive database community.

Predicting biodegradation products and pathways

MOTIVATION Current methods for the prediction of biodegradation products and pathways of organic environmental pollutants either do not take into account domain knowledge or do not provide probability estimates. In this article, we propose a hybrid knowledge- and machine learning-based approach to overcome these limitations in the context of the University of Minnesota Pathway Prediction System (UM-PPS). The proposed solution performs relative reasoning in a machine learning framework, and obtains one probability estimate for each biotransformation rule of the system. As the application of a rule then depends on a threshold for the probability estimate, the trade-off between recall (sensitivity) and precision (selectivity) can be addressed and leveraged in practice. RESULTS Results from leave-one-out cross-validation show that a recall and precision of approximately 0.8 can be achieved for a subset of 13 transformation rules. Therefore, it is possible to optimize precision without compromising recall. We are currently integrating the results into an experimental version of the UM-PPS server. AVAILABILITY The program is freely available on the web at http://wwwkramer.in.tum.de/research/applications/biodegradation/data. CONTACT kramer@in.tum.de.

enviPath – The environmental contaminant biotransformation pathway resource

The University of Minnesota Biocatalysis/Biodegradation Database and Pathway Prediction System (UM-BBD/PPS) has been a unique resource covering microbial biotransformation pathways of primarily xenobiotic chemicals for over 15 years. This paper introduces the successor system, enviPath (The Environmental Contaminant Biotransformation Pathway Resource), which is a complete redesign and reimplementation of UM-BBD/PPS. enviPath uses the database from the UM-BBD/PPS as a basis, extends the use of this database, and allows users to include their own data to support multiple use cases. Relative reasoning is supported for the refinement of predictions and to allow its extensions in terms of previously published, but not implemented machine learning models. User access is simplified by providing a REST API that simplifies the inclusion of enviPath into existing workflows. An RDF database is used to enable simple integration with other databases. enviPath is publicly available at https://envipath.org with free and open access to its core data.

Multi-label classification using boolean matrix decomposition

This paper introduces a new multi-label classifier based on Boolean matrix decomposition. Boolean matrix decomposition is used to extract, from the full label matrix, latent labels representing useful Boolean combinations of the original labels. Base level models predict latent labels, which are subsequently transformed into the actual labels by Boolean matrix multiplication with the second matrix from the decomposition. The new method is tested on six publicly available datasets with varying numbers of labels. The experimental evaluation shows that the new method works particularly well on datasets with a large number of labels and strong dependencies among them.

SINDBAD and SiQL: An Inductive Database and Query Language in the Relational Model

In this demonstration, we will present the concepts and an implementation of an inductive database--- as proposed by Imielinski and Mannila --- in the relational model. The goal is to support all steps of the knowledge discovery process on the basis of queries to a database system. The query language SiQL (structured inductive query language), an SQL extension, offers query primitives for feature selection, discretization, pattern mining, clustering, instance-based learning and rule induction. A prototype system processing such queries was implemented as part of the SINDBAD (structured inductive database development) project. To support the analysis of multi-relational data, we incorporated multi-relational distance measures based on set distances and recursive descent. The inclusion of rule-based classification models made it necessary to extend the data model and software architecture significantly. The prototype is applied to three different data sets: gene expression analysis, gene regulation prediction and structure-activity relationships (SARs) of small molecules.

Cinema Data Mining: The Smell of Fear

While the physiological response of humans to emotional events or stimuli is well-investigated for many modalities (like EEG, skin resistance, ...), surprisingly little is known about the exhalation of so-called Volatile Organic Compounds (VOCs) at quite low concentrations in response to such stimuli. VOCs are molecules of relatively small mass that quickly evaporate or sublimate and can be detected in the air that surrounds us. The paper introduces a new field of application for data mining, where trace gas responses of people reacting on-line to films shown in cinemas (or movie theaters) are related to the semantic content of the films themselves. To do so, we measured the VOCs from a movie theater over a whole month in intervals of thirty seconds, and annotated the screened films by a controlled vocabulary compiled from multiple sources. To gain a better understanding of the data and to reveal unknown relationships, we have built prediction models for so-called forward prediction (the prediction of future VOCs from the past), backward prediction (the prediction of past scene labels from future VOCs), which is some form of abductive reasoning, and Granger causality. Experimental results show that some VOCs and some labels can be predicted with relatively low error, and that hint for causality with low p-values can be detected in the data. The data set is publicly available at: https://github.com/jorro/smelloffear.

An inductive database and query language in the relational model

In the demonstration, we will present the concepts and an implementation of an inductive database -- as proposed by Imielinski and Mannila -- in the relational model. The goal is to support all steps of the knowledge discovery process, from pre-processing via data mining to post-processing, on the basis of queries to a database system. The query language SIQL (structured inductive query language), an SQL extension, offers query primitives for feature selection, discretization, pattern mining, clustering, instance-based learning and rule induction. A prototype system processing such queries was implemented as part of the SINDBAD (structured inductive database development) project. Key concepts of this system, among others, are the closure of operators and distances between objects. To support the analysis of multi-relational data, we incorporated multi-relational distance measures based on set distances and recursive descent. The inclusion of rule-based classification models made it necessary to extend the data model and the software architecture significantly. The prototype is applied to three different applications: gene expression analysis, gene regulation prediction and structure-activity relationships (SARs) of small molecules.

A Nonlinear Label Compression and Transformation Method for Multi-label Classification Using Autoencoders

Multi-label classification targets the prediction of multiple interdependent and non-exclusive binary target variables. Transformation-based algorithms transform the data set such that regular single-label algorithms can be applied to the problem. A special type of transformation-based classifiers are label compression methods, which compress the labels and then mostly use single label classifiers to predict the compressed labels. So far, there are no compression-based algorithms that follow a problem transformation approach and address non-linear dependencies in the labels. In this paper, we propose a new algorithm, called Maniac (Multi-lAbel classificatioN usIng AutoenCoders), which extracts the non-linear dependencies by compressing the labels using autoencoders. We adapt the training process of autoencoders in a way to make them more suitable for a parameter optimization in the context of this algorithm. The method is evaluated on eight standard multi-label data sets. Experiments show that despite not producing a good ranking, Maniac generates a particularly good bipartition of the labels into positives and negatives. This is caused by rather strong predictions with either really high or low probability. Additionally, the algorithm seems to perform better given more labels and a higher label cardinality in the data set.