3,134 publications from this institution
Abstract Single-nucleotide variants (SNVs) are the most common variations in the human genome. Recently developed methods for SNV detection from single-cell DNA sequencing (scDNAseq) data, such as SCIΦ and scVILP, leverage the evolutionary history of the cells to overcome the technical errors associated with single-cell sequencing protocols. Despite being accurate, these methods are not scalable to the extensive genomic breadth of single-cell whole-genome (scWGS) and whole-exome sequencing (scWES) data. Here we report on a new scalable method, Phylovar, which extends the phylogeny-guided variant calling approach to sequencing datasets containing millions of loci. Through benchmarking on simulated datasets under different settings, we show that, Phylovar outperforms SCIΦ in terms of running time while being more accurate than Monovar (which is not phylogeny-aware) in terms of SNV detection. Furthermore, we applied Phylovar to two real biological datasets: an scWES triple-negative breast cancer data consisting of 32 cells and 3375 loci as well as an scWGS data of neuron cells from a normal human brain containing 16 cells and approximately 2.5 million loci. For the cancer data, Phylovar detected somatic SNVs with high or moderate functional impact that were also supported by bulk sequencing dataset and for the neuron dataset, Phylovar identified 5745 SNVs with non-synonymous effects some of which were associated with neurodegenerative diseases. We implemented Phylovar and made it publicly available at https://github.com/mae6/Phylovar.git .
Objective To evaluate the degree of peripheral vasodilation induced by dexmedetomidine and midazolam in the patients undergoing lower extremity surgery. Methods One hundred patients of both sexes, aged 27-64 yr, with body mass index of 20-30 kg/m2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective lower extremity surgery under epidural anesthesia, were randomly divided into 4 groups(n=25 each): dexmedetomidine group(group D), compensatory volume expansion+ dexmedetomidine group(group CVE+ D), midazolam group(group M), and compensatory volume expansion + midazolam group(group CVE+ M). In D and CVE+ D groups, dexmedetomidine was infused over 5 min in a loading dose of 0.5 μg/kg, followed by an infusion of 0.3-0.6 μg·kg-1·h-1 until Observer's Assessment of Alertness/Sedation (OAA/S)score reached 3.In M and CVE+ M groups, midazolam was injected over 5 min in a dose of 0.05 mg/kg, followed by an infusion of 0.03-0.10 μg·kg-1·h-1 until OAA/S score reached 3.In CVE+ D and CVE+ M groups, compensatory volume expansion was performed at the same time as dexmedetomidine and midazolam were infused, 6% hydroxyethyl starch 130/0.4 and sodium chloride solution was infused intravenously at a rate of 0.5 ml·kg-1·min-1, and the total volume infused was 7 ml/kg.Before injection of dexmedetomidine or midazolam, and when OAA/S score reached 3, arterial blood samples were collected to determine the blood glucose concentration.Then 50% glucose 10 ml was injected intravenously, and 3 min later, arterial blood samples were collected again to determine the blood glucose concentration.According to the initial distribution volume of glucose, the degree of glucose dilution was determined to reflect the degree of peripheral vasodilation. Results The degree of peripheral vasodilation was(8.5±0.5)%, (8.4±0.4)%, (0.9±0.5)% and(0.8±0.5)% in D, CVE+ D, M and CVE+ M groups, respectively.There was no significant difference in the degree of peripheral vasodilation between D and CVE+ D groups, and between M and CVE+ M groups. Conclusion The degree of peripheral vasodilation induced by dexmedetomidine is about 8.5%, and by midazolam is only about 0.9% in the patients undergoing lower extremity surgery. Key words: Dexmedetomidine; Midazolam; Conscious sedation; Peripheral vasodilation
METAPOP (http://webs.uvigo.es/anpefi/metapop/) is a desktop application that provides an analysis of gene and allelic diversity in subdivided populations from molecular genotype or coancestry data as well as a tool for the management of genetic diversity in conservation programs. A partition of gene and allelic diversity is made within and between subpopulations, in order to assess the contribution of each subpopulation to global diversity for descriptive population genetics or conservation purposes. In the context of management of subdivided populations in in situ conservation programs, the software also determines the optimal contributions (i.e., number of offspring) of each individual, the number of migrants, and the particular subpopulations involved in the exchange of individuals in order to maintain the largest level of gene diversity in the whole population with a desired control in the rate of inbreeding. The partition of gene and allelic diversity within and between subpopulations is illustrated with microsatellite and SNP data from human populations.
The use of ambulatory blood pressure (BP) monitoring (ABPM) has provided a method of BP assessment that compensates for some of the limitations of conventional office values. Elimination of the “white-coat” effect is among the described advantages of ABPM. However, differences between consecutive days of monitoring in patients wearing the device for the first but not for the second and successive times [Hermida et al. Am J Hypertens. 2001;14:34], suggest a pressor response to ABPM. We have evaluated the extent and duration of this “ABPM effect” in normotensive subjects. We studied 170 volunteers (117 men), 23.2±3.7 (mean±SD) years of age, without medical history of hypertension and diurnal BP mean from ABPM consistently below 135/85 for systolic/diastolic BP. Subjects underwent ABPM at 30-minute intervals for 48 consecutive hours in up to six different occasions within 2 years, yielding 515 BP profiles. Circadian parameters established by population multiple-component analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204] were compared among consecutive days of monitoring by nonparametric testing. In normotensive volunteers evaluated for the first time, results indicate a highly significant (P<0.001) reduction during the second day of monitoring as compared to the first in the diurnal, but not in the nocturnal mean, of systolic and diastolic BP. This pressor effect increases BP on the average by a significant 4 and 3 mm Hg for systolic and diastolic BP for the first 4 hours of measurement. This effect can be documented as statistically significant independently of gender or day of the week of monitoring. The pressor effect was almost double in subjects who started ABPM in the evening (after 13:00 hours) as compared to subjects who started monitoring in the morning. This “ABPM effect” cannot be observed when the same subjects were evaluated for the second or successive times 3 months apart. ABPM for 48 consecutive hours in normotensive subjects reveals a statistically significant pressor response that could reflect a novelty effect in the use of the monitoring device for the first time, and that cannot be due just to regression to the mean. This “ABPM effect”, much higher in hypertensive patients [Hermida et al. Am J Hypertens. 2001;14:34], should be taken into consideration for a proper diagnosis of hypertension and evaluation of treatment efficacy by the use of ABPM. DGES, PM98-0106; PGICT00-PXI-32205PN; University of Vigo.
Abstract Several strategies have been proposed to assign substitution models in phylogenomic datasets, or partitioning. The accuracy of these methods, and most importantly, their impact on phylogenetic estimation has not been thoroughly assessed using computer simulations. We simulated multiple partitioning scenarios to benchmark two a priori partitioning schemes (one model for the whole alignment, one model for each data block), and two statistical approaches (hierarchical clustering and greedy) implemented in PartitionFinder and in our new program, PartitionTest. Most methods were able to identify optimal partitioning schemes closely related to the true one. Greedy algorithms identified the true partitioning scheme more frequently than the clustering algorithms, but selected slightly less accurate partitioning schemes and tended to underestimate the number of partitions. PartitionTest was several times faster than PartitionFinder, with equal or better accuracy. Importantly, maximum likelihood phylogenetic inference was very robust to the partitioning scheme. Best-fit partitioning schemes resulted in optimal phylogenetic performance, without appreciable differences compared to the use of the true partitioning scheme. However, accurate trees were also obtained by a “simple” strategy consisting of assigning independent GTR+G models to each data block. On the contrary, leaving the data unpartitioned always diminished the quality of the trees inferred, to a greater or lesser extent depending on the simulated scenario. The analysis of empirical data confirmed these trends, although suggesting a stronger influence of the partitioning scheme. Overall, our results suggests that statistical partitioning, but also the a priori assignment of independent GTR+G models, maximize phylogenomic performance.
Computer simulations were used to investigate the efficiency of management methods for the conservation of a structured population when local adaptation exists. A subdivided population, with subpopulations adapted to different optima for a quantitative trait under stabilizing selection, was managed in order to maintain the highest genetic diversity in a 10-generation period. Two procedures were compared. For the first, minimum coancestry contributions were carried out independently for each subpopulation, and random migration of individuals was accomplished thereafter. For the second, minimum coancestry contributions from individuals were globally implemented, including an optimal migration design. This optimal method can be adjusted to control local inbreeding to different extents. Adaptation to local optima implies a reduction in the efficiency of the management methods because of the effective failure in the established migrations. For strong selection, the optimal design can be very inefficient, even more than the random migration scheme because the intended migrants have usually low fitness in the recipient subpopulations. However, for more realistic moderate or weak selection, the optimal method is more efficient than random migration, especially if inbreeding depression on fitness is also taken into account. It is concluded that the optimal management method can be recommended in conservation programs with local adaptation of subpopulations, but this issue should be accounted for when designing the management strategies.
We studied sequence variation in 16S rDNA in 204 individuals from 37 populations of the land snail Candidula unifasciata (Poiret 1801) across the core species range in France, Switzerland, and Germany. Phylogeographic, nested clade, and coalescence analyses were used to elucidate the species evolutionary history. The study revealed the presence of two major evolutionary lineages that evolved in separate refuges in southeast France as result of previous fragmentation during the Pleistocene. Applying a recent extension of the nested clade analysis (Templeton 2001), we inferred that range expansions along river valleys in independent corridors to the north led eventually to a secondary contact zone of the major clades around the Geneva Basin. There is evidence supporting the idea that the formation of the secondary contact zone and the colonization of Germany might be postglacial events. The phylogeographic history inferred for C. unifasciata differs from general biogeographic patterns of postglacial colonization previously identified for other taxa, and it might represent a common model for species with restricted dispersal.