Infantile Convulsions with Paroxysmal Dyskinesia (ICCA Syndrome) and Copy Number Variation at Human Chromosome 16p11

BACKGROUND: Benign infantile convulsions and paroxysmal dyskinesia are episodic cerebral disorders that can share common genetic bases. They can be co-inherited as one single autosomal dominant trait (ICCA syndrome); the disease ICCA gene maps at chromosome 16p12-q12. Despite intensive and conventional mutation screening, the ICCA gene remains unknown to date. The critical area displays highly complicated genomic architecture and is the site of deletions and duplications associated with various diseases. The possibility that the ICCA syndrome is related to the existence of large-scale genomic alterations was addressed in the present study. METHODOLOGY/PRINCIPAL FINDINGS: A combination of whole genome and dedicated oligonucleotide array comparative genomic hybridization coupled with quantitative polymerase chain reaction was used. Low copy number of a region corresponding to a genomic variant (Variation_7105) located at 16p11 nearby the centromere was detected with statistical significance at much higher frequency in patients from ICCA families than in ethnically matched controls. The genomic variant showed no apparent difference in size and copy number between patients and controls, making it very unlikely that the genomic alteration detected here is ICCA-specific. Furthermore, no other genomic alteration that would directly cause the ICCA syndrome in those nine families was detected in the ICCA critical area. CONCLUSIONS/SIGNIFICANCE: Our data excluded that inherited genomic deletion or duplication events directly cause the ICCA syndrome; rather, they help narrowing down the critical ICCA region dramatically and indicate that the disease ICCA genetic defect lies very close to or within Variation_7105 and hence should now be searched in the corresponding genomic area and its surrounding regions

Elite Bases Regression: A Real-time Algorithm for Symbolic Regression

Symbolic regression is an important but challenging research topic in data mining. It can detect the underlying mathematical models. Genetic programming (GP) is one of the most popular methods for symbolic regression. However, its convergence speed might be too slow for large scale problems with a large number of variables. This drawback has become a bottleneck in practical applications. In this paper, a new non-evolutionary real-time algorithm for symbolic regression, Elite Bases Regression (EBR), is proposed. EBR generates a set of candidate basis functions coded with parse-matrix in specific mapping rules. Meanwhile, a certain number of elite bases are preserved and updated iteratively according to the correlation coefficients with respect to the target model. The regression model is then spanned by the elite bases. A comparative study between EBR and a recent proposed machine learning method for symbolic regression, Fast Function eXtraction (FFX), are conducted. Numerical results indicate that EBR can solve symbolic regression problems more effectively.Comment: The 2017 13th International Conference on Natural Computation, Fuzzy Systems and Knowledge Discovery (ICNC-FSKD 2017

FVQA: Fact-based Visual Question Answering

Visual Question Answering (VQA) has attracted a lot of attention in both Computer Vision and Natural Language Processing communities, not least because it offers insight into the relationships between two important sources of information. Current datasets, and the models built upon them, have focused on questions which are answerable by direct analysis of the question and image alone. The set of such questions that require no external information to answer is interesting, but very limited. It excludes questions which require common sense, or basic factual knowledge to answer, for example. Here we introduce FVQA, a VQA dataset which requires, and supports, much deeper reasoning. FVQA only contains questions which require external information to answer. We thus extend a conventional visual question answering dataset, which contains image-question-answerg triplets, through additional image-question-answer-supporting fact tuples. The supporting fact is represented as a structural triplet, such as . We evaluate several baseline models on the FVQA dataset, and describe a novel model which is capable of reasoning about an image on the basis of supporting facts.Comment: 16 page

Science and Technology Cooperation in Cross-border Regions::A Proximity Approach with Evidence for Northern Europe

Given the sheer number of cross-border regions (CBRs) within the EU, their socio-economic importance has been recognized both by policy-makers and academics. Recently, the novel concept of cross-border regional innovation system has been introduced to guide the assessment of integration processes in CBRs. A central focus of this concept is set on analyzing the impact of varying types of proximity (cognitive, technological, etc.) on cross-border cooperation. Previous empirical applications of the concept have, however, relied on individual case studies and varying methodologies, thus complicating and constraining comparisons between different CBRs. Here a broader view is provided by comparing 28 Northern European CBRs. The empirical analysis utilizes economic, science and technology (S&T) statistics to construct proximity indicators and measures S&T integration in the context of cross-border cooperation. The findings from descriptive statistics and exploratory count data regressions show that technological and cognitive proximity measures are significantly related to S&T cooperation activities (cross-border co-publications and co-patents). Taken together, our empirical approach underlines the feasibility of utilizing the proximity approach for comparative analyses in CBR settings

Identifying statistical dependence in genomic sequences via mutual information estimates

Questions of understanding and quantifying the representation and amount of information in organisms have become a central part of biological research, as they potentially hold the key to fundamental advances. In this paper, we demonstrate the use of information-theoretic tools for the task of identifying segments of biomolecules (DNA or RNA) that are statistically correlated. We develop a precise and reliable methodology, based on the notion of mutual information, for finding and extracting statistical as well as structural dependencies. A simple threshold function is defined, and its use in quantifying the level of significance of dependencies between biological segments is explored. These tools are used in two specific applications. First, for the identification of correlations between different parts of the maize zmSRp32 gene. There, we find significant dependencies between the 5' untranslated region in zmSRp32 and its alternatively spliced exons. This observation may indicate the presence of as-yet unknown alternative splicing mechanisms or structural scaffolds. Second, using data from the FBI's Combined DNA Index System (CODIS), we demonstrate that our approach is particularly well suited for the problem of discovering short tandem repeats, an application of importance in genetic profiling.Comment: Preliminary version. Final version in EURASIP Journal on Bioinformatics and Systems Biology. See http://www.hindawi.com/journals/bsb

A comparative study on global wavelet and polynomial models for nonlinear regime-switching systems

A comparative study of wavelet and polynomial models for non-linear Regime-Switching (RS) systems is carried out. RS systems, considered in this study, are a class of severely non-linear systems, which exhibit abrupt changes or dramatic breaks in behaviour, due to RS caused by associated events. Both wavelet and polynomial models are used to describe discontinuous dynamical systems, where it is assumed that no a priori information about the inherent model structure and the relative regime switches of the underlying dynamics is known, but only observed input-output data are available. An Orthogonal Least Squares (OLS) algorithm interfered with by an Error Reduction Ratio (ERR) index and regularised by an Approximate Minimum Description Length (AMDL) criterion, is used to construct parsimonious wavelet and polynomial models. The performance of the resultant wavelet models is compared with that of the relative polynomial models, by inspecting the predictive capability of the associated representations. It is shown from numerical results that wavelet models are superior to polynomial models, in respect of generalisation properties, for describing severely non-linear RS systems

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease