Estimating readability with the Strathclyde readability measure

Despite their significant limitations, readability measures that are easy to apply have definite appeal. With this in mind, we have been exploring the prospects for more insightful measures that are computer-based and, thereby, still easily applied. The orthodox reliance on intrinsic syntactic features is an inherent limitation of most readability measures, since they have no reference to the likelihood that readers will be acquainted with the constituent words and phrases. To accommodate this feature of 'human familiarity', we have devised a metric that combines traditional factors, such as Average Sentence Length, with a measure of word 'commonality' based upon word frequency. This paper details the derivation, nature and application of the Strathclyde Readability Measure (SRM)

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Menu-based extensions to GNU Emacs

Extensions to the GNU incarnation of the Emacs editing system which provide facilities for menu-based interaction is given. Following the Emacs philosophy the described system is designed to allow for user-customisation and extension of menus, which are sensitive to the user's editing mode. The system affords pop-up and pull-right menus on SUN workstations and terminal menus on the wide range of terminals supported by Emacs. Additionally, a menu-based menu design tool has been implemented. This provides intelligent support to individual users who wish to construct or alter menus. The operation of this Emacs menu system is outlined and its range of facilities described in detail

Signalling signalhood and the emergence of communication.

a b s t r a c t A unique hallmark of human language is that it uses signals that are both learnt and symbolic. The emergence of such signals was therefore a defining event in human cognitive evolution, yet very little is known about how such a process occurs. Previous work provides some insights on how meaning can become attached to form, but a more foundational issue is presently unaddressed. How does a signal signal its own signalhood? That is, how do humans even know that communicative behaviour is indeed communicative in nature? We introduce an experimental game that has been designed to tackle this problem. We find that it is commonly resolved with a bootstrapping process, and that this process influences the final form of the communication system. Furthermore, sufficient common ground is observed to be integral to the recognition of signalhood, and the emergence of dialogue is observed to be the key step in the development of a system that can be employed to achieve shared goals

Supplementary Material for: A Combined Functional Annotation Score for Non-Synonymous Variants

<i>Aims:</i> Next-generation sequencing has opened the possibility of large-scale sequence-based disease association studies. A major challenge in interpreting whole-exome data is predicting which of the discovered variants are deleterious or neutral. To address this question in silico, we have developed a score called Combined Annotation scoRing toOL (CAROL), which combines information from 2 bioinformatics tools: PolyPhen-2 and SIFT, in order to improve the prediction of the effect of non-synonymous coding variants. <i>Methods:</i> We used a weighted <i>Z</i> method that combines the probabilistic scores of PolyPhen-2 and SIFT. We defined 2 dataset pairs to train and test CAROL using information from the dbSNP: ‘HGMD-PUBLIC’ and 1000 Genomes Project databases. The training pair comprises a total of 980 positive control (disease-causing) and 4,845 negative control (non-disease-causing) variants. The test pair consists of 1,959 positive and 9,691 negative controls.<i> Results:</i> CAROL has higher predictive power and accuracy for the effect of non-synonymous variants than each individual annotation tool (PolyPhen-2 and SIFT) and benefits from higher coverage. <i>Conclusion:</i> The combination of annotation tools can help improve automated prediction of whole-genome/exome non-synonymous variant functional consequences

Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants

Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10-26). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10-36). We demonstrate significant power gains in detecting medical trait associations. © 2014 Macmillan Publishers Limited. All rights reserved

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation