Compressing DNA sequence databases with coil

Background: Publicly available DNA sequence databases such as GenBank are large, and are growing at an exponential rate. The sheer volume of data being dealt with presents serious storage and data communications problems. Currently, sequence data is usually kept in large "flat files," which are then compressed using standard Lempel-Ziv (gzip) compression – an approach which rarely achieves good compression ratios. While much research has been done on compressing individual DNA sequences, surprisingly little has focused on the compression of entire databases of such sequences. In this study we introduce the sequence database compression software coil. Results: We have designed and implemented a portable software package, coil, for compressing and decompressing DNA sequence databases based on the idea of edit-tree coding. coil is geared towards achieving high compression ratios at the expense of execution time and memory usage during compression – the compression time represents a "one-off investment" whose cost is quickly amortised if the resulting compressed file is transmitted many times. Decompression requires little memory and is extremely fast. We demonstrate a 5% improvement in compression ratio over state-of-the-art general-purpose compression tools for a large GenBank database file containing Expressed Sequence Tag (EST) data. Finally, coil can efficiently encode incremental additions to a sequence database. Conclusion: coil presents a compelling alternative to conventional compression of flat files for the storage and distribution of DNA sequence databases having a narrow distribution of sequence lengths, such as EST data. Increasing compression levels for databases having a wide distribution of sequence lengths is a direction for future work

Modelling mitochondrial site polymorphisms to infer the number of segregating units and mutation rate

We present a mathematical model of mitochondrial inheritance evolving under neutral evolution to interpret the heteroplasmies observed at some sites. A comparison of the levels of heteroplasmies transmitted from mother to her offspring allows us to estimate the number Nx of inherited mitochondrial genomes (segregating units). The model demonstrates the necessity of accounting for both the multiplicity of an unknown number Nx, and the threshold θ, below which heteroplasmy cannot be detected reliably, in order to estimate the mitochondrial mutation rate μm in the maternal line of descent. Our model is applicable to pedigree studies of any eukaryotic species where site heteroplasmies are observed in regions of the mitochondria, provided neutrality can be assumed. The model is illustrated with an analysis of site heteroplasmies in the first hypervariable region of mitochondrial sequence data sampled from Adélie penguin families, providing an estimate Nx and μm. This estimate of μm was found to be consistent with earlier estimates from ancient DNA analysis

Validity of evaluative factors from Big Five and HEXACO questionnaires

Highlights • Applied bifactor models to NEO-FFI-3, HEXACO PI-R, and BFI-2 data estimating domain, evaluation, and acquiescence factors. • The evaluation factor was a significant, positive predictor of GPA. • The acquiescence factor was not a strong predictor of GPA.• Domain factor score validities were more negative than corresponding summated scale validities.• Results suggest that extraneous factor contamination can be measured and used with the modeling techniques employed here

Controlled cardiac reoxygenation does not improve myocardial function following global myocardial ischemia

AbstractBackgroundIt has been shown that abrupt re-exposure of ischemic myocardium to oxygen can lead to increased peroxidative damage to myocytes (oxygen paradox). Controlled cardiac reoxygenation, as an adjunct to substrate-enhanced cardioplegia, has been shown to improve myocardial function and limit reperfusion injury when utilizing standardized hyperoxic cardiopulmonary bypass (CPB). The objective of our study was to evaluate the effect of controlled reoxygenation on myocardial function following global ischemia employing normoxic CPB.Study designNineteen female swine (30–40kg) were placed on vented, normoxic CPB. They were subjected to 45–50min of unprotected global ischemia (aortic cross clamping) followed by 30min of controlled cardiac reperfusion utilizing substrate-enhanced cardioplegia. Group 1 maintained normoxic pO2 (O2 tension of 90–110mmHg). In Group 2, reoxygenation was titrated gradually and increased from venous to arterial levels (O2 tensions from 40 to 110mmHg over 15min). We measured coronary sinus blood samples for CK, CK-MB, nitric oxide, and conjugated dienes at baseline, 5min into the cardioplegic resuscitation, 5min after the cross clamp removal, and just prior to the termination of the study. Hearts were pathologically studied and scored for evidence of tissue peroxidation.ResultsAlthough not significantly different, Group 1 (normoxic reperfusion) animals were more likely to wean from CPB (p=0.141) and had a higher mean arterial pressure (p=0.556). In Group 1, conjugated dienes were significantly higher 5min into the resuscitative protocol (p=0.018) and at the termination of bypass (p=0.035). Five of six animals in Group 1 eventually attained normal sinus rhythm as opposed to three out of 13 in Group 2 (p=0.041). There was no significant difference in histology scoring between the two groups for tissue peroxidation.ConclusionThis study of controlled cardiac reoxygenation in a lethal ischemic swine model failed to demonstrate that the use of controlled reoxygenation on the myocardial function following global ischemia was better with maintained normoxic pO2 (with O2 tensions of 90–110mmHg) than when reoxygenation was titrated gradually and increased from venous to arterial levels (O2 tensions from 40 to 110mmHg over 15min)

Phylogenetic Tree Reconstruction Accuracy and Model Fit when Proportions of Variable Sites Change across the Tree

Commonly used phylogenetic models assume a homogeneous process through time in all parts of the tree. However, it is known that these models can be too simplistic as they do not account for nonhomogeneous lineage-specific properties. In particular, it is now widely recognized that as constraints on sequences evolve, the proportion and positions of variable sites can vary between lineages causing heterotachy. The extent to which this model misspecification affects tree reconstruction is still unknown. Here, we evaluate the effect of changes in the proportions and positions of variable sites on model fit and tree estimation. We consider 5 current models of nucleotide sequence evolution in a Bayesian Markov chain Monte Carlo framework as well as maximum parsimony (MP). We show that for a tree with 4 lineages where 2 nonsister taxa undergo a change in the proportion of variable sites tree reconstruction under the best-fitting model, which is chosen using a relative test, often results in the wrong tree. In this case, we found that an absolute test of model fit is a better predictor of tree estimation accuracy. We also found further evidence that MP is not immune to heterotachy. In addition, we show that increased sampling of taxa that have undergone a change in proportion and positions of variable sites is critical for accurate tree reconstruction

Genetic causes of hypercalciuric nephrolithiasis

Renal stone disease (nephrolithiasis) affects 3–5% of the population and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in over 35% of patients and may occur as a monogenic disorder that is more likely to manifest itself in childhood. Studies of these monogenic forms of hypercalciuric nephrolithiasis in humans, e.g. Bartter syndrome, Dent’s disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal disease, is caused by mutations of the bumetanide-sensitive Na–K–Cl (NKCC2) co-transporter, the renal outer-medullary potassium (ROMK) channel, the voltage-gated chloride channel, CLC-Kb, the CLC-Kb beta subunit, barttin, or the calcium-sensing receptor (CaSR). Dent’s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to hypercalciuria and nephrolithiasis

The History, Relevance, and Applications of the Periodic System in Geochemistry

Geochemistry is a discipline in the earth sciences concerned with understanding the chemistry of the Earth and what that chemistry tells us about the processes that control the formation and evolution of Earth materials and the planet itself. The periodic table and the periodic system, as developed by Mendeleev and others in the nineteenth century, are as important in geochemistry as in other areas of chemistry. In fact, systemisation of the myriad of observations that geochemists make is perhaps even more important in this branch of chemistry, given the huge variability in the nature of Earth materials – from the Fe-rich core, through the silicate-dominated mantle and crust, to the volatile-rich ocean and atmosphere. This systemisation started in the eighteenth century, when geochemistry did not yet exist as a separate pursuit in itself. Mineralogy, one of the disciplines that eventually became geochemistry, was central to the discovery of the elements, and nineteenth-century mineralogists played a key role in this endeavour. Early “geochemists” continued this systemisation effort into the twentieth century, particularly highlighted in the career of V.M. Goldschmidt. The focus of the modern discipline of geochemistry has moved well beyond classification, in order to invert the information held in the properties of elements across the periodic table and their distribution across Earth and planetary materials, to learn about the physicochemical processes that shaped the Earth and other planets, on all scales. We illustrate this approach with key examples, those rooted in the patterns inherent in the periodic law as well as those that exploit concepts that only became familiar after Mendeleev, such as stable and radiogenic isotopes