16104731
A Dichotomic Search Algorithm for Mining and Learning in Domain-Specific Logics
Many application domains make use of specific data structures such as sequences and graphs to represent knowledge. These data structures are ill-fitted to the standard representations used in machine learning and data-mining algorithms: propositional representations are not expressive enough, and first order ones are not efficient enough. In order to efficiently represent and reason on these data structures, and the complex patterns that are related to them, we use domain-specific logics. We show these logics can be built by the composition of logical components that model elementary data structures. The standard strategies of top-down and bottom-up search are ill-suited to some of these logics, and lack flexibility. We therefore introduce a dichotomic search strategy, that is analogous to a dichotomic search in an ordered array. We prove this provides more flexibility in the search, while retaining completeness and non-redundancy. We present a novel algorithm for learning using domain specific logics and dichotomic search, and analyse its complexity. We also describe two applications which illustrates the search for motifs in sequences; where these motifs have arbitrary length and length-constrained gaps. In the first application sequences represent the trains of the East-West challenge; in the second application they represent the secondary structure of Yeast proteins for the discrimination of their biological functions.
15579646
BLID: An Application of Logical Information Systems to Bioinformatics
BLID (Bio-Logical Intelligent Database) is a bioinformatic system designed to help biologists extract new knowledge from raw genome data by providing high-level facilities for both data browsing and analysis. We describe BLID’s novel data browsing system which is based on the idea of Logical Information Systems. This enables combined querying and navigation of data in BLID (extracted from public bioinformatic repositories). The browsing language is a logic especially designed for bioinformatics. It currently includes sequence motifs, taxonomies, and macromolecule structures, and it is designed to be easily extensible, as it is composed of reusable components. Navigation is tightly combined with this logic, and assists users in browsing a genome through a form of human-computer dialog.
3055046
Warmr: a data mining tool for chemical data
Data mining techniques are becoming increasingly important in chemistry as databases become too large to examine manually. Data mining methods from the field of Inductive Logic Programming (ILP) have potential advantages for structural chemical data. In this paper we present Warmr, the first ILP data mining algorithm to be applied to chemoinformatic data. We illustrate the value of Warmr by applying it to a well studied database of chemical compounds tested for carcinogenicity in rodents. Data mining was used to find all frequent substructures in the database, and knowledge of these frequent substructures is shown to add value to the database. One use of the frequent substructures was to convert them into probabilistic prediction rules relating compound description to carcinogenesis. These rules were found to be accurate on test data, and to give some insight into the relationship between structure and activity in carcinogenesis. The substructures were also used to prove that there existed no accurate rule, based purely on atom-bond substructure with less than seven conditions, that could predict carcinogenicity. This results put a lower bound on the complexity of the relationship between chemical structure and carcinogenicity. Only by using a data mining algorithm, and by doing a complete search, is it possible to prove such a result. Finally the frequent substructures were shown to add value by increasing the accuracy of statistical and machine learning programs that were trained to predict chemical carcinogenicity. We conclude that Warmr, and ILP data mining methods generally, are an important new tool for analysing chemical databases.
15136247
Knowledge Discovery in Multi-label Phenotype Data
The biological sciences are undergoing an explosion in the amount of available data. New data analysis methods are needed to deal with the data. We present work using KDD to analyse data from mutant phenotype growth experiments with the yeast S. cerevisiae to predict novel gene functions. The analysis of the data presented a number of challenges: multi-class labels, a large number of sparsely populated classes, the need to learn a set of accurate rules (not a complete classification), and a very large amount of missing values. We developed resampling strategies and modified the algorithm C4.5 to deal with these problems. Rules were learnt which are accurate and biologically meaningful. The rules predict function of 83 putative genes of currently unknown function at an estimated accuracy of ≥ 80%.
8206025
Inductive Logic Programming Used to Discover Topological Constraints in Protein Structures
This paper describes the application of the Inductive Logic Programming (ILP) program GOLEM to the discovery of constraints in the packing of beta-sheets in alpha/beta proteins. These constraints (rules) have a role in understanding the protein folding problem. Constraints were learnt for four features of beta-sheet packing: the winding direction of two sequential strands, whether two consecutive strands pack parallel or anti-parallel, whether two strands pack adjacently, and whether a beta-strand is at an edge. Investigation of the learnt constraints revealed interesting patterns, some of which were previously known, others that were novel. Novel features include the discovery: that the relationship between pairs of sequential strands is in general one of decreasing size, and that more sequential pairs of strands wind in the direction out than the direction in. We conclude that machine learning has a useful place in molecular biology as a pattern discovery tool.
16848815
The utility of different representations of protein sequence for predicting functional class
MOTIVATION
Data Mining Prediction (DMP) is a novel approach to predicting protein functional class from sequence. DMP works even in the absence of a homologous protein of known function. We investigate the utility of different ways of representing protein sequence in DMP (residue frequencies, phylogeny, predicted structure) using the Escherichia coli genome as a model.


RESULTS
Using the different representations DMP learnt prediction rules that were more accurate than default at every level of function using every type of representation. The most effective way to represent sequence was using phylogeny (75% accuracy and 13% coverage of unassigned ORFs at the most general level of function: 69% accuracy and 7% coverage at the most detailed). We tested different methods for combining predictions from the different types of representation. These improved both the accuracy and coverage of predictions, e.g. 40% of all unassigned ORFs could be predicted at an estimated accuracy of 60% and 5% of unassigned ORFs could be predicted at an estimated accuracy of 86%.
970544
Machine learning of functional class from phenotype data
MOTIVATION
Mutant phenotype growth experiments are an important novel source of functional genomics data which have received little attention in bioinformatics. We applied supervised machine learning to the problem of using phenotype data to predict the functional class of Open Reading Frames (ORFs) in Saccaromyces cerevisiae. Three sources of data were used: TRansposon-Insertion Phenotypes, Localization and Expression in Saccharomyces (TRIPLES), European Functional Analysis Network (EUROFAN) and Munich Information Center for Protein Sequences (MIPS). The analysis of the data presented a number of challenges to machine learning: multi-class labels, a large number of sparsely populated classes, the need to learn a set of accurate rules (not a complete classification), and a very large amount of missing values. We modified the algorithm C4.5 to deal with these problems.


RESULTS
Rules were learnt which are accurate and biologically meaningful. The rules predict function of 83 ORFs of unknown function at an estimated accuracy of > or = 80%.