## 2017 |
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1. | Latino, Diogo; Wicker, Jörg; Gütlein, Martin; Schmid, Emanuel; Kramer, Stefan; Fenner, Kathrin Eawag-Soil in enviPath: a new resource for exploring regulatory pesticide soil biodegradation pathways and half-life data Journal Article In: Environmental Science: Process & Impact, 2017. Abstract | Links | BibTeX | Altmetric | Tags: biodegradation, cheminformatics, computational sustainability, data mining, enviPath, multi-label classification, REST, web services @article{latino2017eawag, title = {Eawag-Soil in enviPath: a new resource for exploring regulatory pesticide soil biodegradation pathways and half-life data}, author = {Diogo Latino and Jörg Wicker and Martin Gütlein and Emanuel Schmid and Stefan Kramer and Kathrin Fenner}, doi = {10.1039/C6EM00697C}, year = {2017}, date = {2017-01-01}, journal = {Environmental Science: Process & Impact}, publisher = {The Royal Society of Chemistry}, abstract = {Developing models for the prediction of microbial biotransformation pathways and half-lives of trace organic contaminants in different environments requires as training data easily accessible and sufficiently large collections of respective biotransformation data that are annotated with metadata on study conditions. Here, we present the Eawag-Soil package, a public database that has been developed to contain all freely accessible regulatory data on pesticide degradation in laboratory soil simulation studies for pesticides registered in the EU (282 degradation pathways, 1535 reactions, 1619 compounds and 4716 biotransformation half-life values with corresponding metadata on study conditions). We provide a thorough description of this novel data resource, and discuss important features of the pesticide soil degradation data that are relevant for model development. Most notably, the variability of half-life values for individual compounds is large and only about one order of magnitude lower than the entire range of median half-life values spanned by all compounds, demonstrating the need to consider study conditions in the development of more accurate models for biotransformation prediction. We further show how the data can be used to find missing rules relevant for predicting soil biotransformation pathways. From this analysis, eight examples of reaction types were presented that should trigger the formulation of new biotransformation rules, e.g., Ar-OH methylation, or the extension of existing rules e.g., hydroxylation in aliphatic rings. The data were also used to exemplarily explore the dependence of half-lives of different amide pesticides on chemical class and experimental parameters. This analysis highlighted the value of considering initial transformation reactions for the development of meaningful quantitative-structure biotransformation relationships (QSBR), which is a novel opportunity of f ered by the simultaneous encoding of transformation reactions and corresponding half-lives in Eawag-Soil. Overall, Eawag-Soil provides an unprecedentedly rich collection of manually extracted and curated biotransformation data, which should be useful in a great variety of applications.}, keywords = {biodegradation, cheminformatics, computational sustainability, data mining, enviPath, multi-label classification, REST, web services}, pubstate = {published}, tppubtype = {article} } Developing models for the prediction of microbial biotransformation pathways and half-lives of trace organic contaminants in different environments requires as training data easily accessible and sufficiently large collections of respective biotransformation data that are annotated with metadata on study conditions. Here, we present the Eawag-Soil package, a public database that has been developed to contain all freely accessible regulatory data on pesticide degradation in laboratory soil simulation studies for pesticides registered in the EU (282 degradation pathways, 1535 reactions, 1619 compounds and 4716 biotransformation half-life values with corresponding metadata on study conditions). We provide a thorough description of this novel data resource, and discuss important features of the pesticide soil degradation data that are relevant for model development. Most notably, the variability of half-life values for individual compounds is large and only about one order of magnitude lower than the entire range of median half-life values spanned by all compounds, demonstrating the need to consider study conditions in the development of more accurate models for biotransformation prediction. We further show how the data can be used to find missing rules relevant for predicting soil biotransformation pathways. From this analysis, eight examples of reaction types were presented that should trigger the formulation of new biotransformation rules, e.g., Ar-OH methylation, or the extension of existing rules e.g., hydroxylation in aliphatic rings. The data were also used to exemplarily explore the dependence of half-lives of different amide pesticides on chemical class and experimental parameters. This analysis highlighted the value of considering initial transformation reactions for the development of meaningful quantitative-structure biotransformation relationships (QSBR), which is a novel opportunity of f ered by the simultaneous encoding of transformation reactions and corresponding half-lives in Eawag-Soil. Overall, Eawag-Soil provides an unprecedentedly rich collection of manually extracted and curated biotransformation data, which should be useful in a great variety of applications. | |

## 2016 |
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2. | Wicker, Jörg; Fenner, Kathrin; Kramer, Stefan A Hybrid Machine Learning and Knowledge Based Approach to Limit Combinatorial Explosion in Biodegradation Prediction Incollection In: Lässig, Jörg; Kersting, Kristian; Morik, Katharina (Ed.): Computational Sustainability, pp. 75-97, Springer International Publishing, Cham, 2016, ISBN: 978-3-319-31858-5. Abstract | Links | BibTeX | Altmetric | Tags: biodegradation, cheminformatics, computational sustainability, enviPath, machine learning, metabolic pathways, multi-label classification @incollection{wicker2016ahybrid, title = {A Hybrid Machine Learning and Knowledge Based Approach to Limit Combinatorial Explosion in Biodegradation Prediction}, author = {Jörg Wicker and Kathrin Fenner and Stefan Kramer}, editor = {Jörg Lässig and Kristian Kersting and Katharina Morik}, url = {http://dx.doi.org/10.1007/978-3-319-31858-5_5}, doi = {10.1007/978-3-319-31858-5_5}, isbn = {978-3-319-31858-5}, year = {2016}, date = {2016-04-21}, booktitle = {Computational Sustainability}, pages = {75-97}, publisher = {Springer International Publishing}, address = {Cham}, abstract = {One of the main tasks in chemical industry regarding the sustainability of a product is the prediction of its environmental fate, i.e., its degradation products and pathways. 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 chapter, we propose a hybrid knowledge-based 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. Since 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 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. The set of used rules is further extended using multi-label classification, where dependencies among the transformation rules are exploited to improve the predictions. While the results regarding recall and precision vary, the area under the ROC curve can be improved using multi-label classification. Therefore, it is possible to optimize precision without compromising recall. Recently, we integrated the presented approach into enviPath, a complete redesign and re-implementation of UM-PPS.}, keywords = {biodegradation, cheminformatics, computational sustainability, enviPath, machine learning, metabolic pathways, multi-label classification}, pubstate = {published}, tppubtype = {incollection} } One of the main tasks in chemical industry regarding the sustainability of a product is the prediction of its environmental fate, i.e., its degradation products and pathways. 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 chapter, we propose a hybrid knowledge-based 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. Since 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 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. The set of used rules is further extended using multi-label classification, where dependencies among the transformation rules are exploited to improve the predictions. While the results regarding recall and precision vary, the area under the ROC curve can be improved using multi-label classification. Therefore, it is possible to optimize precision without compromising recall. Recently, we integrated the presented approach into enviPath, a complete redesign and re-implementation of UM-PPS. | |

3. | Wicker, Jörg; Tyukin, Andrey; Kramer, Stefan A Nonlinear Label Compression and Transformation Method for Multi-Label Classification using Autoencoders Inproceedings In: Bailey, James; Khan, Latifur; Washio, Takashi; Dobbie, Gill; Huang, Zhexue Joshua; Wang, Ruili (Ed.): The 20th Pacific Asia Conference on Knowledge Discovery and Data Mining (PAKDD), pp. 328-340, Springer International Publishing, Switzerland, 2016, ISBN: 978-3-319-31753-3. Abstract | Links | BibTeX | Altmetric | Tags: autoencoders, label compression, machine learning, multi-label classification @inproceedings{wicker2016nonlinear, title = {A Nonlinear Label Compression and Transformation Method for Multi-Label Classification using Autoencoders}, author = {Jörg Wicker and Andrey Tyukin and Stefan Kramer}, editor = {James Bailey and Latifur Khan and Takashi Washio and Gill Dobbie and Zhexue Joshua Huang and Ruili Wang}, url = {http://dx.doi.org/10.1007/978-3-319-31753-3_27}, doi = {10.1007/978-3-319-31753-3_27}, isbn = {978-3-319-31753-3}, year = {2016}, date = {2016-04-16}, booktitle = {The 20th Pacific Asia Conference on Knowledge Discovery and Data Mining (PAKDD)}, volume = {9651}, pages = {328-340}, publisher = {Springer International Publishing}, address = {Switzerland}, series = {Lecture Notes in Computer Science}, abstract = {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, that compress the labels and then mostly use single label classifiers to predict the compressed labels. So far, there are no compression-based algorithms 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.}, keywords = {autoencoders, label compression, machine learning, multi-label classification}, pubstate = {published}, tppubtype = {inproceedings} } 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, that compress the labels and then mostly use single label classifiers to predict the compressed labels. So far, there are no compression-based algorithms 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. | |

4. | Wicker, Jörg; Lorsbach, Tim; Gütlein, Martin; Schmid, Emanuel; Latino, Diogo; Kramer, Stefan; Fenner, Kathrin enviPath - The Environmental Contaminant Biotransformation Pathway Resource Journal Article In: Nucleic Acid Research, 44 (D1), pp. D502-D508, 2016. Abstract | Links | BibTeX | Altmetric | Tags: biodegradation, cheminformatics, computational sustainability, data mining, enviPath, linked data, machine learning, metabolic pathways, multi-label classification @article{wicker2016envipath, title = {enviPath - The Environmental Contaminant Biotransformation Pathway Resource}, author = {Jörg Wicker and Tim Lorsbach and Martin Gütlein and Emanuel Schmid and Diogo Latino and Stefan Kramer and Kathrin Fenner}, editor = {Michael Galperin}, url = {http://nar.oxfordjournals.org/content/44/D1/D502.abstract}, doi = {10.1093/nar/gkv1229}, year = {2016}, date = {2016-01-01}, journal = {Nucleic Acid Research}, volume = {44}, number = {D1}, pages = {D502-D508}, abstract = {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.}, keywords = {biodegradation, cheminformatics, computational sustainability, data mining, enviPath, linked data, machine learning, metabolic pathways, multi-label classification}, pubstate = {published}, tppubtype = {article} } 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. | |

## 2013 |
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5. | Wicker, Jörg Large Classifier Systems in Bio- and Cheminformatics PhD Thesis Technische Universität München, 2013. Abstract | Links | BibTeX | Tags: biodegradation, bioinformatics, cheminformatics, computational sustainability, data mining, enviPath, machine learning, multi-label classification, multi-relational learning, toxicity @phdthesis{wicker2013large, title = {Large Classifier Systems in Bio- and Cheminformatics}, author = {Jörg Wicker}, url = {http://mediatum.ub.tum.de/node?id=1165858}, year = {2013}, date = {2013-01-01}, school = {Technische Universität München}, abstract = {Large classifier systems are machine learning algorithms that use multiple classifiers to improve the prediction of target values in advanced classification tasks. Although learning problems in bio- and cheminformatics commonly provide data in schemes suitable for large classifier systems, they are rarely used in these domains. This thesis introduces two new classifiers incorporating systems of classifiers using Boolean matrix decomposition to handle data in a schema that often occurs in bio- and cheminformatics. The first approach, called MLC-BMaD (multi-label classification using Boolean matrix decomposition), uses Boolean matrix decomposition to decompose the labels in a multi-label classification task. The decomposed matrices are a compact representation of the information in the labels (first matrix) and the dependencies among the labels (second matrix). The first matrix is used in a further multi-label classification while the second matrix is used to generate the final matrix from the predicted values of the first matrix. MLC-BMaD was evaluated on six standard multi-label data sets, the experiments showed that MLC-BMaD can perform particularly well on data sets with a high number of labels and a small number of instances and can outperform standard multi-label algorithms. Subsequently, MLC-BMaD is extended to a special case of multi-relational learning, by considering the labels not as simple labels, but instances. The algorithm, called ClassFact (Classification factorization), uses both matrices in a multi-label classification. Each label represents a mapping between two instances. Experiments on three data sets from the domain of bioinformatics show that ClassFact can outperform the baseline method, which merges the relations into one, on hard classification tasks. Furthermore, large classifier systems are used on two cheminformatics data sets, the first one is used to predict the environmental fate of chemicals by predicting biodegradation pathways. The second is a data set from the domain of predictive toxicology. In biodegradation pathway prediction, I extend a knowledge-based system and incorporate a machine learning approach to predict a probability for biotransformation products based on the structure- and knowledge-based predictions of products, which are based on transformation rules. The use of multi-label classification improves the performance of the classifiers and extends the number of transformation rules that can be covered. For the prediction of toxic effects of chemicals, I applied large classifier systems to the ToxCasttexttrademark data set, which maps toxic effects to chemicals. As the given toxic effects are not easy to predict due to missing information and a skewed class distribution, I introduce a filtering step in the multi-label classification, which finds labels that are usable in multi-label prediction and does not take the others in the prediction into account. Experiments show that this approach can improve upon the baseline method using binary classification, as well as multi-label approaches using no filtering. The presented results show that large classifier systems can play a role in future research challenges, especially in bio- and cheminformatics, where data sets frequently consist of more complex structures and data can be rather small in terms of the number of instances compared to other domains.}, keywords = {biodegradation, bioinformatics, cheminformatics, computational sustainability, data mining, enviPath, machine learning, multi-label classification, multi-relational learning, toxicity}, pubstate = {published}, tppubtype = {phdthesis} } Large classifier systems are machine learning algorithms that use multiple classifiers to improve the prediction of target values in advanced classification tasks. Although learning problems in bio- and cheminformatics commonly provide data in schemes suitable for large classifier systems, they are rarely used in these domains. This thesis introduces two new classifiers incorporating systems of classifiers using Boolean matrix decomposition to handle data in a schema that often occurs in bio- and cheminformatics. The first approach, called MLC-BMaD (multi-label classification using Boolean matrix decomposition), uses Boolean matrix decomposition to decompose the labels in a multi-label classification task. The decomposed matrices are a compact representation of the information in the labels (first matrix) and the dependencies among the labels (second matrix). The first matrix is used in a further multi-label classification while the second matrix is used to generate the final matrix from the predicted values of the first matrix. MLC-BMaD was evaluated on six standard multi-label data sets, the experiments showed that MLC-BMaD can perform particularly well on data sets with a high number of labels and a small number of instances and can outperform standard multi-label algorithms. Subsequently, MLC-BMaD is extended to a special case of multi-relational learning, by considering the labels not as simple labels, but instances. The algorithm, called ClassFact (Classification factorization), uses both matrices in a multi-label classification. Each label represents a mapping between two instances. Experiments on three data sets from the domain of bioinformatics show that ClassFact can outperform the baseline method, which merges the relations into one, on hard classification tasks. Furthermore, large classifier systems are used on two cheminformatics data sets, the first one is used to predict the environmental fate of chemicals by predicting biodegradation pathways. The second is a data set from the domain of predictive toxicology. In biodegradation pathway prediction, I extend a knowledge-based system and incorporate a machine learning approach to predict a probability for biotransformation products based on the structure- and knowledge-based predictions of products, which are based on transformation rules. The use of multi-label classification improves the performance of the classifiers and extends the number of transformation rules that can be covered. For the prediction of toxic effects of chemicals, I applied large classifier systems to the ToxCasttexttrademark data set, which maps toxic effects to chemicals. As the given toxic effects are not easy to predict due to missing information and a skewed class distribution, I introduce a filtering step in the multi-label classification, which finds labels that are usable in multi-label prediction and does not take the others in the prediction into account. Experiments show that this approach can improve upon the baseline method using binary classification, as well as multi-label approaches using no filtering. The presented results show that large classifier systems can play a role in future research challenges, especially in bio- and cheminformatics, where data sets frequently consist of more complex structures and data can be rather small in terms of the number of instances compared to other domains. | |

## 2012 |
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6. | Wicker, Jörg; Pfahringer, Bernhard; Kramer, Stefan Multi-label Classification Using Boolean Matrix Decomposition Inproceedings In: Proceedings of the 27th Annual ACM Symposium on Applied Computing, pp. 179–186, ACM, 2012, ISBN: 978-1-4503-0857-1. Abstract | Links | BibTeX | Altmetric | Tags: associations, Boolean matrix decomposition, machine learning, multi-label classification @inproceedings{wicker2012multi, title = {Multi-label Classification Using Boolean Matrix Decomposition}, author = {Jörg Wicker and Bernhard Pfahringer and Stefan Kramer}, url = {https://wicker.nz/nwp-acm/authorize.php?id=N10032 http://doi.acm.org/10.1145/2245276.2245311}, doi = {10.1145/2245276.2245311}, isbn = {978-1-4503-0857-1}, year = {2012}, date = {2012-01-01}, booktitle = {Proceedings of the 27th Annual ACM Symposium on Applied Computing}, pages = {179--186}, publisher = {ACM}, series = {SAC '12}, abstract = {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.}, keywords = {associations, Boolean matrix decomposition, machine learning, multi-label classification}, pubstate = {published}, tppubtype = {inproceedings} } 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. |

## 2017 |
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1. | Eawag-Soil in enviPath: a new resource for exploring regulatory pesticide soil biodegradation pathways and half-life data Journal Article In: Environmental Science: Process & Impact, 2017. | |

## 2016 |
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2. | A Hybrid Machine Learning and Knowledge Based Approach to Limit Combinatorial Explosion in Biodegradation Prediction Incollection In: Lässig, Jörg; Kersting, Kristian; Morik, Katharina (Ed.): Computational Sustainability, pp. 75-97, Springer International Publishing, Cham, 2016, ISBN: 978-3-319-31858-5. | |

3. | A Nonlinear Label Compression and Transformation Method for Multi-Label Classification using Autoencoders Inproceedings In: Bailey, James; Khan, Latifur; Washio, Takashi; Dobbie, Gill; Huang, Zhexue Joshua; Wang, Ruili (Ed.): The 20th Pacific Asia Conference on Knowledge Discovery and Data Mining (PAKDD), pp. 328-340, Springer International Publishing, Switzerland, 2016, ISBN: 978-3-319-31753-3. | |

4. | enviPath - The Environmental Contaminant Biotransformation Pathway Resource Journal Article In: Nucleic Acid Research, 44 (D1), pp. D502-D508, 2016. | |

## 2013 |
||

5. | Large Classifier Systems in Bio- and Cheminformatics PhD Thesis Technische Universität München, 2013. | |

## 2012 |
||

6. | Multi-label Classification Using Boolean Matrix Decomposition Inproceedings In: Proceedings of the 27th Annual ACM Symposium on Applied Computing, pp. 179–186, ACM, 2012, ISBN: 978-1-4503-0857-1. |