A new procedure for determining the genetic basis of a physiological process in a non-model species, illustrated by cold induced angiogenesis in the carp

<p>Abstract</p> <p>Background</p> <p>Physiological processes occur in many species for which there is yet no sequenced genome and for which we would like to identify the genetic basis. For example, some species increase their vascular network to minimise the effects of reduced oxygen diffusion and increased blood viscosity associated with low temperatures. Since many angiogenic and endothelial genes have been discovered in man, functional homolog relationships between carp, zebrafish and human were used to predict the genetic basis of cold-induced angiogenesis in <it>Cyprinus Carpio </it>(carp). In this work, carp sequences were collected and built into contigs. Human-carp functional homolog relationships were derived via zebrafish using a new Conditional Stepped Reciprocal Best Hit (CSRBH) protocol. Data sources including publications, Gene Ontology and cDNA libraries were then used to predict the identity of known or potential angiogenic genes. Finally, re-analyses of cold carp microarray data identified carp genes up-regulated in response to low temperatures in heart and muscle.</p> <p>Results</p> <p>The CSRBH approach outperformed all other methods and attained 8,726 carp to human functional homolog relationships for 16,650 contiguous sequences. This represented 3,762 non-redundant genes and 908 of them were predicted to have a role in angiogenesis. The total number of up-regulated differentially expressed genes was 698 and 171 of them were putatively angiogenic. Of these, 5 genes representing the functional homologs NCL, RHOA, MMP9, GRN and MAPK1 are angiogenesis-related genes expressed in response to low temperature.</p> <p>Conclusion</p> <p>We show that CSRBH functional homologs relationships and re-analyses of gene expression data can be combined in a non-model species to predict genes of biological interest before a genome sequence is fully available. Programs to run these analyses locally are available from <url>http://www.cbrg.ox.ac.uk/~jherbert/</url>.</p

Uncovering exceptional predictions using exploratory analysis of second stage machine learning.

Nowadays, algorithmic systems for making decisions are widely used to facilitate decisions in a variety of fields such as medicine, banking, applying for universities or network security. However, many machine learning algorithms are well-known for their complex mathematical internal workings which turn them into black boxes and makes their decision-making process usually difficult to understand even for experts. In this thesis, we try to develop a methodology to explain why a certain exceptional machine learned decision was made incorrectly by using the interpretability of the decision tree classifier. Our approach can provide insights about potential flaws in feature definition or completeness, as well as potential incorrect training data and outliers. It also promises to help find the stereotypes learned by machine learning algorithms which lead to incorrect predictions and especially, to prevent discrimination in making socially sensitive decisions, such as credit decisions as well as crime-related and policing predictions

An extensive experimental evaluation of automated machine learning methods for recommending classification algorithms

This paper presents an experimental comparison among four automated machine learning (AutoML) methods for recommending the best classification algorithm for a given input dataset. Three of these methods are based on evolutionary algorithms (EAs), and the other is Auto-WEKA, a well-known AutoML method based on the combined algorithm selection and hyper-parameter optimisation (CASH) approach. The EA-based methods build classification algorithms from a single machine learning paradigm: either decision-tree induction, rule induction, or Bayesian network classification. Auto-WEKA combines algorithm selection and hyper-parameter optimisation to recommend classification algorithms from multiple paradigms. We performed controlled experiments where these four AutoML methods were given the same runtime limit for different values of this limit. In general, the difference in predictive accuracy of the three best AutoML methods was not statistically significant. However, the EA evolving decision-tree induction algorithms has the advantage of producing algorithms that generate interpretable classification models and that are more scalable to large datasets, by comparison with many algorithms from other learning paradigms that can be recommended by Auto-WEKA. We also observed that Auto-WEKA has shown meta-overfitting, a form of overfitting at the meta-learning level, rather than at the base-learning level

A Survey Of Methods For Explaining Black Box Models

In the last years many accurate decision support systems have been constructed as black boxes, that is as systems that hide their internal logic to the user. This lack of explanation constitutes both a practical and an ethical issue. The literature reports many approaches aimed at overcoming this crucial weakness sometimes at the cost of scarifying accuracy for interpretability. The applications in which black box decision systems can be used are various, and each approach is typically developed to provide a solution for a specific problem and, as a consequence, delineating explicitly or implicitly its own definition of interpretability and explanation. The aim of this paper is to provide a classification of the main problems addressed in the literature with respect to the notion of explanation and the type of black box system. Given a problem definition, a black box type, and a desired explanation this survey should help the researcher to find the proposals more useful for his own work. The proposed classification of approaches to open black box models should also be useful for putting the many research open questions in perspective.Comment: This work is currently under review on an international journa

A survey of methods for explaining black box models

In recent years, many accurate decision support systems have been constructed as black boxes, that is as systems that hide their internal logic to the user. This lack of explanation constitutes both a practical and an ethical issue. The literature reports many approaches aimed at overcoming this crucial weakness, sometimes at the cost of sacrificing accuracy for interpretability. The applications in which black box decision systems can be used are various, and each approach is typically developed to provide a solution for a specific problem and, as a consequence, it explicitly or implicitly delineates its own definition of interpretability and explanation. The aim of this article is to provide a classification of the main problems addressed in the literature with respect to the notion of explanation and the type of black box system. Given a problem definition, a black box type, and a desired explanation, this survey should help the researcher to find the proposals more useful for his own work. The proposed classification of approaches to open black box models should also be useful for putting the many research open questions in perspective

Improving the hierarchical classification of protein functions With swarm intelligence

This thesis investigates methods to improve the performance of hierarchical classification. In terms of this thesis hierarchical classification is a form of supervised learning, where the classes in a data set are arranged in a tree structure. As a base for our new methods we use the TDDC (top-down divide-and-conquer) approach for hierarchical classification, where each classifier is built only to discriminate between sibling classes. Firstly, we propose a swarm intelligence technique which varies the types of classifiers used at each divide within the TDDC tree. Our technique, PSO/ACO-CS (Particle Swarm Optimisation/Ant Colony Optimisation Classifier Selection), finds combinations of classifiers to be used in the TDDC tree using the global search ability of PSO/ACO. Secondly, we propose a technique that attempts to mitigate a major drawback of the TDDC approach. The drawback is that if at any point in the TDDC tree an example is misclassified it can never be correctly classified further down the TDDC tree. Our approach, PSO/ACO-RO (PSO/ACO-Recovery Optimisation) decides whether to redirect examples at a given classifier node using, again, the global search ability of PSO/ACO. Thirdly, we propose an ensemble based technique, HEHRS (Hierarchical Ensembles of Hierarchical Rule Sets), which attempts to boost the accuracy at each classifier node in the TDDC tree by using information from classifiers (rule sets) in the rest of that tree. We use Particle Swarm Optimisation to weight the individual rules within each ensemble. We evaluate these three new methods in hierarchical bioinformatics datasets that we have created for this research. These data sets represent the real world problem of protein function prediction. We find through extensive experimentation that the three proposed methods improve upon the baseline TDDC method to varying degrees. Overall the HEHRS and PSO/ACO- CS-RO approaches are most effective, although they are associated with a higher computational cost

Automatically evolving rule induction algorithms with grammar-based genetic programming

In the last 30 years, research in the field of rule induction algorithms produced a large number of algorithms. However, these algorithms are usually obtained from the combination of a basic rule induction algorithm (typically following the sequential covering approach) with new evaluation functions, pruning methods and stopping criteria for refining or producing rules, generating many "new" and more sophisticated sequential covering algorithms. We cannot deny that these attempts to improve the basic sequential covering approach have succeeded. Hence, if manually changing these major components of rule induction algorithms can result in new, significantly better ones, why not to automate this process to make it more cost-effective? This is the core idea of this work: to automate the process of designing rule induction algorithms by means of grammar-based genetic programming. Grammar-based Genetic Programming (GGP) is a special type of evolutionary algorithm used to automatically evolve computer programs. The most interesting feature of this type of algorithm is that it incorporates a grammar into its search mechanism, which expresses prior knowledge about the problem being solved. Since we have a lot of previous knowledge about how humans design rule induction algorithms, this type of algorithm is intuitively a suitable tool to automatically evolve rule induction algorithms. The grammar given to the proposed GGP system includes knowledge about how humans- design rule induction algorithms, and also presents some new elements which could work in rule induction algorithms, but to the best of our knowledge were not previously tested. The GG P system aims to evolve rule induction algorithms under two different frameworks, as follows. In the first framework, the GGP is used to evolve robust rule induction algorithms, i.e., algorithms which were designed to be applied to virtually any classification data set, like a manually-designed rule induction algorithm. In the second framework, the GGP is applied to evolve rule induction algorithms tailored to a specific application XVI domain, i.e., rule induction algorithms tailored to a single data set. Note that the latter framework is hardly feasible on a hard scale in the case of conventional, manually-designed algorithms, since the number of classification data sets greatly outnumbers the number of rule induction algorithms designers. However, it is clearly feasible on a large scale when using the proposed system, which automates the process of rule induction algorithm design and implementation. Overall, extensive computational experiments with 20 VCI data sets and 5 bioinformatics data sets showed that effective rule induction algorithms can be automatically generated using the GGP in both frameworks. Moreover, the automatically evolved rule induction algorithms were shown to be competitive with (and overall slightly better than) four well-known manually designed rule induction algorithms when comparing their predictive accuracies. The proposed GGP system was also compared to a grammar-based hillclimbing system, and experimental results showed that the GGP system is a more effective method to evolve rule induction algorithms than the grammar-based hillclimbing method. At last, a multi-objective version of the GGP (based on the concept of Pareto dominance) was also proposed, and experiments were performed to evolve robust rule induction algorithms which generate both accurate and simple models. The results showed that in most of the cases the GGP system can produce rule induction algorithms which are competitive in predictive accuracy to wellknown human-designed rule induction algorithms, but generate simpler classification modes - i.e., smaller rule sets, intuitively easier to be interpreted by the user

Predicting Post-Synaptic Activity in Proteins with Data Mining

The bioinformatics problem being addressed in this paper is to predict whether or not a protein has post-synaptic activity. This problem is of great intrinsic interest because proteins with post-synaptic activities are connected with functioning of the nervous system. Indeed, many proteins having post-synaptic activity have been functionally characterized by biochemical, immunological and proteomic exercises. They represent a wide variety of proteins with functions in extracellular signal reception and propagation through intracellular apparatuses, cell adhesion molecules and scaffolding proteins that link them in a web. The challenge is to automatically discover features of the primary sequences of proteins that typically occur in proteins with post-synaptic activity but rarely (or never) occur in proteins without post-synaptic activity, and vice-versa. In this context, we used data mining to automatically discover classification rules that predict whether or not a protein has post-synaptic activity. The discovered rules were analysed with respect to their predictive accuracy (generalization ability) and with respect to their interestingness to biologists (in the sense of representing novel, unexpected knowledge)