Allele mining strategies: principles and utilisation for blast resistance genes in rice (Oryza sativa L.)

Allele mining is a promising way to dissect naturally occurring allelic variants of candidate genes with essential agronomic qualities. With the identification, isolation and characterisation of blast resistance genes in rice, it is now possible to dissect the actual allelic variants of these genes within an array of rice cultivars via allele mining. Multiple alleles from the complex locus serve as a reservoir of variation to generate functional genes. The routine sequence exchange is one of the main mechanisms of R gene evolution and development. Allele mining for resistance genes can be an important method to identify additional resistance alleles and new haplotypes along with the development of allele-specific markers for use in marker-assisted selection. Allele mining can be visualised as a vital link between effective utilisation of genetic and genomic resources in genomics-driven modern plant breeding. This review studies the actual concepts and potential of mining approaches for the discovery of alleles and their utilisation for blast resistance genes in rice. The details provided here will be important to provide the rice breeder with a worthwhile introduction to allele mining and its methodology for breakthrough discovery of fresh alleles hidden in hereditary diversity, which is vital for crop improvement

SolRgene: an online database to explore disease resistance genes in tuber-bearing Solanum species

Background The cultivated potato (Solanum tuberosum L.) is an important food crop, but highly susceptible to many pathogens. The major threat to potato production is the Irish famine pathogen Phytophthora infestans, which causes the devastating late blight disease. Potato breeding makes use of germplasm from wild relatives (wild germplasm) to introduce resistances into cultivated potato. The Solanum section Petota comprises tuber-bearing species that are potential donors of new disease resistance genes. The aim of this study was to explore Solanum section Petota for resistance genes and generate a widely accessible resource that is useful for studying and implementing disease resistance in potato. Description The SolRgene database contains data on resistance to P. infestans and presence of R genes and R gene homologues in Solanum section Petota. We have explored Solanum section Petota for resistance to late blight in high throughput disease tests under various laboratory conditions and in field trials. From resistant wild germplasm, segregating populations were generated and assessed for the presence of resistance genes. All these data have been entered into the SolRgene database. To facilitate genetic and resistance gene evolution studies, phylogenetic data of the entire SolRgene collection are included, as well as a tool for generating phylogenetic trees of selected groups of germplasm. Data from resistance gene allele-mining studies are incorporated, which enables detection of R gene homologs in related germplasm. Using these resources, various resistance genes have been detected and some of these have been cloned, whereas others are in the cloning pipeline. All this information is stored in the online SolRgene database, which allows users to query resistance data, sequences, passport data of the accessions, and phylogenic classifications. Conclusion Solanum section Petota forms the basis of the SolRgene database, which contains a collection of resistance data of an unprecedented size and precision. Complemented with R gene sequence data and phylogenetic tools, SolRgene can be considered the primary resource for information on R genes from potato and wild tuber-bearing relatives

Prediction of peptides binding to MHC class I alleles by partial periodic pattern mining

MHC (Major Histocompatibility Complex) is a key player in the immune response of an organism. It is important to be able to predict which antigenic peptides will bind to a spe-cific MHC allele and which will not, creating possibilities for controlling immune response and for the applications of immunotherapy. However a problem encountered in the computational binding prediction methods for MHC class I is the presence of bulges and loops in the peptides, changing the total length. Most machine learning methods in use to-day require the sequences to be of same length to success-fully mine the binding motifs. We propose the use of time-based data mining methods in motif mining to be able to mine motifs position-independently. Also, the information for both binding and non-binding peptides are used on the contrary to the other methods which only rely on binding peptides. The prediction results are between 70-80% for the tested alleles

Prediction of peptides binding to MHC class I alleles by partial periodic pattern mining

MHC (Major Histocompatibility Complex) is a key player in the immune response of an organism. It is important to be able to predict which antigenic peptides will bind to a specific MHC allele and which will not, creating possibilities for controlling immune response and for the applications of immunotherapy. However, a problem for MHC class I is the presence of bulges and loops in the peptides, changing the total length. Most machine learning methods in use today require the sequences to be of same length to successfully mine the binding motifs. We propose the use of time-based data mining methods in motif mining to be able to mine motifs position-independently. Also, the information for both binding and non-binding peptides is used on the contrary to the other methods which only rely on binding peptides. The prediction results are between 60-95% for the tested alleles

WormBase - Nematode Biology and Genomes

WormBase is the major public online database resource for the _Caenorhabditis_ research community. The database was developed primarily for the nematode _C. elegans_ but expanded to host genomes and biological data from other closely related nematode species including _C. briggsae_, _C. remanei_, _C. brenneri_, _C. japonica_ and _Pristionchus pacificus_. WormBase has developed tools to mine the data held within the database and compare the hosted species. Over the years we have developed a variety of curation pipelines which often begin in a "first-pass" literature curation step. This involves a brief overview of the literature before directing it to specialised data curators who extract all relevant information. Curators focus on particular data types or experimental techniques such as gene structure changes (see the Sequence curation poster), variations, phenotypes or RNAi and their expertise in these fields make curation efficient. WormBase works with many other groups and consortiums to validate, process and integrate both large and small scale data resources. WormBase also provides data that will be of interest to the wider biomedical and bioinformatics communities allowing researchers to utilise the information and techniques offered by nematodes to study wider aspects including medicine and disease.
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Text mining meets community curation: a newly designed curation platform to improve author experience and participation at WormBase

Biological knowledgebases rely on expert biocuration of the research literature to maintain up-to-date collections of data organized in machine-readable form. To enter information into knowledgebases, curators need to follow three steps: (i) identify papers containing relevant data, a process called triaging; (ii) recognize named entities; and (iii) extract and curate data in accordance with the underlying data models. WormBase (WB), the authoritative repository for research data on Caenorhabditis elegans and other nematodes, uses text mining (TM) to semi-automate its curation pipeline. In addition, WB engages its community, via an Author First Pass (AFP) system, to help recognize entities and classify data types in their recently published papers. In this paper, we present a new WB AFP system that combines TM and AFP into a single application to enhance community curation. The system employs string-searching algorithms and statistical methods (e.g. support vector machines (SVMs)) to extract biological entities and classify data types, and it presents the results to authors in a web form where they validate the extracted information, rather than enter it de novo as the previous form required. With this new system, we lessen the burden for authors, while at the same time receive valuable feedback on the performance of our TM tools. The new user interface also links out to specific structured data submission forms, e.g. for phenotype or expression pattern data, giving the authors the opportunity to contribute a more detailed curation that can be incorporated into WB with minimal curator review. Our approach is generalizable and could be applied to additional knowledgebases that would like to engage their user community in assisting with the curation. In the five months succeeding the launch of the new system, the response rate has been comparable with that of the previous AFP version, but the quality and quantity of the data received has greatly improved

Automatic categorization of diverse experimental information in the bioscience literature

Background: Curation of information from bioscience literature into biological knowledge databases is a crucial way of capturing experimental information in a computable form. During the biocuration process, a critical first step is to identify from all published literature the papers that contain results for a specific data type the curator is interested in annotating. This step normally requires curators to manually examine many papers to ascertain which few contain information of interest and thus, is usually time consuming. We developed an automatic method for identifying papers containing these curation data types among a large pool of published scientific papers based on the machine learning method Support Vector Machine (SVM). This classification system is completely automatic and can be readily applied to diverse experimental data types. It has been in use in production for automatic categorization of 10 different experimental datatypes in the biocuration process at WormBase for the past two years and it is in the process of being adopted in the biocuration process at FlyBase and the Saccharomyces Genome Database (SGD). We anticipate that this method can be readily adopted by various databases in the biocuration community and thereby greatly reducing time spent on an otherwise laborious and demanding task. We also developed a simple, readily automated procedure to utilize training papers of similar data types from different bodies of literature such as C. elegans and D. melanogaster to identify papers with any of these data types for a single database. This approach has great significance because for some data types, especially those of low occurrence, a single corpus often does not have enough training papers to achieve satisfactory performance. Results: We successfully tested the method on ten data types from WormBase, fifteen data types from FlyBase and three data types from Mouse Genomics Informatics (MGI). It is being used in the curation work flow at WormBase for automatic association of newly published papers with ten data types including RNAi, antibody, phenotype, gene regulation, mutant allele sequence, gene expression, gene product interaction, overexpression phenotype, gene interaction, and gene structure correction. Conclusions: Our methods are applicable to a variety of data types with training set containing several hundreds to a few thousand documents. It is completely automatic and, thus can be readily incorporated to different workflow at different literature-based databases. We believe that the work presented here can contribute greatly to the tremendous task of automating the important yet labor-intensive biocuration effort

A Genetic Programming Framework for Two Data Mining Tasks: Classification and Generalized Rule Induction

This paper proposes a genetic programming (GP) framework for two major data mining tasks, namely classification and generalized rule induction. The framework emphasizes the integration between a GP algorithm and relational database systems. In particular, the fitness of individuals is computed by submitting SQL queries to a (parallel) database server. Some advantages of this integration from a data mining viewpoint are scalability, data-privacy control and automatic parallelization

Mining Pure, Strict Epistatic Interactions from High-Dimensional Datasets: Ameliorating the Curse of Dimensionality

Background: The interaction between loci to affect phenotype is called epistasis. It is strict epistasis if no proper subset of the interacting loci exhibits a marginal effect. For many diseases, it is likely that unknown epistatic interactions affect disease susceptibility. A difficulty when mining epistatic interactions from high-dimensional datasets concerns the curse of dimensionality. There are too many combinations of SNPs to perform an exhaustive search. A method that could locate strict epistasis without an exhaustive search can be considered the brass ring of methods for analyzing high-dimensional datasets. Methodology/Findings: A SNP pattern is a Bayesian network representing SNP-disease relationships. The Bayesian score for a SNP pattern is the probability of the data given the pattern, and has been used to learn SNP patterns. We identified a bound for the score of a SNP pattern. The bound provides an upper limit on the Bayesian score of any pattern that could be obtained by expanding a given pattern. We felt that the bound might enable the data to say something about the promise of expanding a 1-SNP pattern even when there are no marginal effects. We tested the bound using simulated datasets and semi-synthetic high-dimensional datasets obtained from GWAS datasets. We found that the bound was able to dramatically reduce the search time for strict epistasis. Using an Alzheimer's dataset, we showed that it is possible to discover an interaction involving the APOE gene based on its score because of its large marginal effect, but that the bound is most effective at discovering interactions without marginal effects. Conclusions/Significance: We conclude that the bound appears to ameliorate the curse of dimensionality in high-dimensional datasets. This is a very consequential result and could be pivotal in our efforts to reveal the dark matter of genetic disease risk from high-dimensional datasets. © 2012 Jiang, Neapolitan