Object-Oriented Paradigms for Modelling Vascular\ud Tumour Growth: a Case Study

Motivated by a family of related hybrid multiscale models, we have built an object-oriented framework for developing and implementing multiscale models of vascular tumour growth. The models are implemented in our framework as a case study to highlight how object-oriented programming techniques and good object-oriented design may be used effectively to develop hybrid multiscale models of vascular tumour growth. The intention is that this paper will serve as a useful reference for researchers modelling complex biological systems and that these researchers will employ some of the techniques presented herein in their own projects

SODA: Generating SQL for Business Users

The purpose of data warehouses is to enable business analysts to make better decisions. Over the years the technology has matured and data warehouses have become extremely successful. As a consequence, more and more data has been added to the data warehouses and their schemas have become increasingly complex. These systems still work great in order to generate pre-canned reports. However, with their current complexity, they tend to be a poor match for non tech-savvy business analysts who need answers to ad-hoc queries that were not anticipated. This paper describes the design, implementation, and experience of the SODA system (Search over DAta Warehouse). SODA bridges the gap between the business needs of analysts and the technical complexity of current data warehouses. SODA enables a Google-like search experience for data warehouses by taking keyword queries of business users and automatically generating executable SQL. The key idea is to use a graph pattern matching algorithm that uses the metadata model of the data warehouse. Our results with real data from a global player in the financial services industry show that SODA produces queries with high precision and recall, and makes it much easier for business users to interactively explore highly-complex data warehouses.Comment: VLDB201

Using GWAS Data to Identify Copy Number Variants Contributing to Common Complex Diseases

Copy number variants (CNVs) account for more polymorphic base pairs in the human genome than do single nucleotide polymorphisms (SNPs). CNVs encompass genes as well as noncoding DNA, making these polymorphisms good candidates for functional variation. Consequently, most modern genome-wide association studies test CNVs along with SNPs, after inferring copy number status from the data generated by high-throughput genotyping platforms. Here we give an overview of CNV genomics in humans, highlighting patterns that inform methods for identifying CNVs. We describe how genotyping signals are used to identify CNVs and provide an overview of existing statistical models and methods used to infer location and carrier status from such data, especially the most commonly used methods exploring hybridization intensity. We compare the power of such methods with the alternative method of using tag SNPs to identify CNV carriers. As such methods are only powerful when applied to common CNVs, we describe two alternative approaches that can be informative for identifying rare CNVs contributing to disease risk. We focus particularly on methods identifying de novo CNVs and show that such methods can be more powerful than case-control designs. Finally we present some recommendations for identifying CNVs contributing to common complex disorders.Comment: Published in at http://dx.doi.org/10.1214/09-STS304 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

A practical approximation algorithm for solving massive instances of hybridization number for binary and nonbinary trees

Reticulate events play an important role in determining evolutionary relationships. The problem of computing the minimum number of such events to explain discordance between two phylogenetic trees is a hard computational problem. Even for binary trees, exact solvers struggle to solve instances with reticulation number larger than 40-50. Here we present CycleKiller and NonbinaryCycleKiller, the first methods to produce solutions verifiably close to optimality for instances with hundreds or even thousands of reticulations. Using simulations, we demonstrate that these algorithms run quickly for large and difficult instances, producing solutions that are very close to optimality. As a spin-off from our simulations we also present TerminusEst, which is the fastest exact method currently available that can handle nonbinary trees: this is used to measure the accuracy of the NonbinaryCycleKiller algorithm. All three methods are based on extensions of previous theoretical work and are publicly available. We also apply our methods to real data

Kevlar: A Mapping-Free Framework for Accurate Discovery of De Novo Variants.

De novo genetic variants are an important source of causative variation in complex genetic disorders. Many methods for variant discovery rely on mapping reads to a reference genome, detecting numerous inherited variants irrelevant to the phenotype of interest. To distinguish between inherited and de novo variation, sequencing of families (parents and siblings) is commonly pursued. However, standard mapping-based approaches tend to have a high false-discovery rate for de novo variant prediction. Kevlar is a mapping-free method for de novo variant discovery, based on direct comparison of sequences between related individuals. Kevlar identifies high-abundance k-mers unique to the individual of interest. Reads containing these k-mers are partitioned into disjoint sets by shared k-mer content for variant calling, and preliminary variant predictions are sorted using a probabilistic score. We evaluated Kevlar on simulated and real datasets, demonstrating its ability to detect both de novo single-nucleotide variants and indels with high accuracy

Efficient Discovery of Ontology Functional Dependencies

Poor data quality has become a pervasive issue due to the increasing complexity and size of modern datasets. Constraint based data cleaning techniques rely on integrity constraints as a benchmark to identify and correct errors. Data values that do not satisfy the given set of constraints are flagged as dirty, and data updates are made to re-align the data and the constraints. However, many errors often require user input to resolve due to domain expertise defining specific terminology and relationships. For example, in pharmaceuticals, 'Advil' \emph{is-a} brand name for 'ibuprofen' that can be captured in a pharmaceutical ontology. While functional dependencies (FDs) have traditionally been used in existing data cleaning solutions to model syntactic equivalence, they are not able to model broader relationships (e.g., is-a) defined by an ontology. In this paper, we take a first step towards extending the set of data quality constraints used in data cleaning by defining and discovering \emph{Ontology Functional Dependencies} (OFDs). We lay out theoretical and practical foundations for OFDs, including a set of sound and complete axioms, and a linear inference procedure. We then develop effective algorithms for discovering OFDs, and a set of optimizations that efficiently prune the search space. Our experimental evaluation using real data show the scalability and accuracy of our algorithms.Comment: 12 page