HoCHC: A Refutationally Complete and Semantically Invariant System of Higher-order Logic Modulo Theories

We present a simple resolution proof system for higher-order constrained Horn clauses (HoCHC) - a system of higher-order logic modulo theories - and prove its soundness and refutational completeness w.r.t. the standard semantics. As corollaries, we obtain the compactness theorem and semi-decidability of HoCHC for semi-decidable background theories, and we prove that HoCHC satisfies a canonical model property. Moreover a variant of the well-known translation from higher-order to 1st-order logic is shown to be sound and complete for HoCHC in standard semantics. We illustrate how to transfer decidability results for (fragments of) 1st-order logic modulo theories to our higher-order setting, using as example the Bernays-Schonfinkel-Ramsey fragment of HoCHC modulo a restricted form of Linear Integer Arithmetic

RLE Plots: Visualising Unwanted Variation in High Dimensional Data

Unwanted variation can be highly problematic and so its detection is often crucial. Relative log expression (RLE) plots are a powerful tool for visualising such variation in high dimensional data. We provide a detailed examination of these plots, with the aid of examples and simulation, explaining what they are and what they can reveal. RLE plots are particularly useful for assessing whether a procedure aimed at removing unwanted variation, i.e. a normalisation procedure, has been successful. These plots, while originally devised for gene expression data from microarrays, can also be used to reveal unwanted variation in many other kinds of high dimensional data, where such variation can be problematic.Comment: 9 pages, 3 figure

Relationships between estimated autozygosity and complex traits in the UK Biobank

<div><p>Inbreeding increases the risk of certain Mendelian disorders in humans but may also reduce fitness through its effects on complex traits and diseases. Such inbreeding depression is thought to occur due to increased homozygosity at causal variants that are recessive with respect to fitness. Until recently it has been difficult to amass large enough sample sizes to investigate the effects of inbreeding depression on complex traits using genome-wide single nucleotide polymorphism (SNP) data in population-based samples. Further, it is difficult to infer causation in analyses that relate degree of inbreeding to complex traits because confounding variables (e.g., education) may influence both the likelihood for parents to outbreed and offspring trait values. The present study used runs of homozygosity in genome-wide SNP data in up to 400,000 individuals in the UK Biobank to estimate the proportion of the autosome that exists in autozygous tracts—stretches of the genome which are identical due to a shared common ancestor. After multiple testing corrections and controlling for possible sociodemographic confounders, we found significant relationships in the predicted direction between estimated autozygosity and three of the 26 traits we investigated: age at first sexual intercourse, fluid intelligence, and forced expiratory volume in 1 second. Our findings corroborate those of several published studies. These results may imply that these traits have been associated with Darwinian fitness over evolutionary time. However, some of the autozygosity-trait relationships were attenuated after controlling for background sociodemographic characteristics, suggesting that alternative explanations for these associations have not been eliminated. Care needs to be taken in the design and interpretation of ROH studies in order to glean reliable information about the genetic architecture and evolutionary history of complex traits.</p></div