QSdpR: Viral quasispecies reconstruction via correlation clustering

RNA viruses are characterized by high mutation rates that give rise to populations of closely related genomes, known as viral quasispecies. Underlying heterogeneity enables the quasispecies to adapt to changing conditions and proliferate over the course of an infection. Determining genetic diversity of a virus (i.e., inferring haplotypes and their proportions in the population) is essential for understanding its mutation patterns, and for effective drug developments. Here, we present QSdpR, a method and software for the reconstruction of quasispecies from short sequencing reads. The reconstruction is achieved by solving a correlation clustering problem on a read-similarity graph and the results of the clustering are used to estimate frequencies of sub-species; the number of sub-species is determined using pseudo F index. Extensive tests on both synthetic datasets and experimental HIV-1 and Zika virus data demonstrate that QSdpR compares favorably to existing methods in terms of various performance metrics.     

福建省蝴蝶新记录及新订正种

本报道福建省新记录及新订正蝴蝶11种，记叙它们的形态特征、采集地、采集生境及采集时间。     

Improving sandwich variance estimation for marginal Cox analysis of cluster randomized trials

Cluster randomized trials (CRTs) frequently recruit a small number of clusters, therefore necessitating the application of small-sample corrections for valid inference. A recent systematic review indicated that CRTs reporting right-censored, time-to-event outcomes are not uncommon and that the marginal Cox proportional hazards model is one of the common approaches used for primary analysis. While small-sample corrections have been studied under marginal models with continuous, binary, and count outcomes, no prior research has been devoted to the development and evaluation of bias-corrected sandwich variance estimators when clustered time-to-event outcomes are analyzed by the marginal Cox model. To improve current practice, we propose nine bias-corrected sandwich variance estimators for the analysis of CRTs using the marginal Cox model and report on a simulation study to evaluate their small-sample properties. Our results indicate that the optimal choice of bias-corrected sandwich variance estimator for CRTs with survival outcomes can depend on the variability of cluster sizes and can also slightly differ whether it is evaluated according to relative bias or type I error rate. Finally, we illustrate the new variance estimators in a real-world CRT where the conclusion about intervention effectiveness differs depending on the use of small-sample bias corrections. The proposed sandwich variance estimators are implemented in an R package CoxBcv .     

Addressing the influence of instrument surface heat exchange on the measurements of CO2 flux from open-path gas analyzers

There is a growing concern in the flux community that using the eddy covariance method with open‐path CO₂ analyzers often leads to measurements of an apparent ecosystem CO₂ uptake during off‐season periods, especially in cold climates. Such uptake has not been observed when measurements were made with closed‐path analyzers, chambers, or profile methods, suggesting it is an artifact due in some way to the use of open‐path analyzers. In this study, a series of laboratory tests and field experiments were conducted to determine the magnitude of the instrument surface heat exchange in the open path and its relationship with the measured CO₂ flux. Results showed that (1) the surface of an open‐path instrument became substantially warmer than ambient due to electronics and radiation load during daytime, while at night, radiative cooling moderated temperature increases in the path; (2) high‐frequency temperature measurements inside the path were correlated with vertical wind speed producing sensible heat flux inside the instrument path exceeding the ambient heat flux by up to 14%; (3) enclosing the open‐path instrument eliminated the sensible heat flux in the path, and caused measured CO₂ flux to match a closed‐path reference; (4) using sensible heat flux measured directly inside the open path in the WPL term instead of the ambient sensible heat flux also led to a match in CO₂ flux between open‐path instrument and closed‐path reference; and (5) correcting previously collected open‐path CO₂ flux data was possible by estimating the instrument heating effect with a semi‐empirical model using standard weather variables. Results showed that all proposed techniques led to a significant reduction in apparent CO₂ uptake during off‐season periods and to a reduction of the underestimation of CO₂ release in other periods. Close agreement between the open‐path measurements and closed‐path references was achieved in all cases.     

Evaluating the accuracy of geometrical distortion correction of magnetic resonance images for use in intracranial brain tumor radiotherapy

AimDetermine the 1) effectiveness of correction for gradient-non-linearity and susceptibility effects on both QUASAR GRID^3D and CIRS phantoms; and 2) the magnitude and location of regions of residual distortion before and after correction.BackgroundUsing magnetic resonance imaging (MRI) as a primary dataset for radiotherapy planning requires correction for geometrical distortion and non-uniform intensity.Materials and MethodsPhantom Study: MRI, computed tomography (CT) and cone beam CT images of QUASAR GRID^3D and CIRS head phantoms were acquired. Patient Study: Ten patients were MRI-scanned for stereotactic radiosurgery treatment. Correction algorithm: Two magnitude and one phase difference image were acquired to create a field map. A MATLAB program was used to calculate geometrical distortion in the frequency encoding direction, and 3D interpolation was applied to resize it to match 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images. MPRAGE images were warped according to the interpolated field map in the frequency encoding direction. The corrected and uncorrected MRI images were fused, deformable registered, and a difference distortion map generated.ResultsMaximum deviation improvements: GRID^3D, 0.27 mm y-direction, 0.07 mm z-direction, 0.23 mm x-direction. CIRS, 0.34 mm, 0.1 mm and 0.09 mm at 20-, 40- and 60-mm diameters from the isocenter. Patient data show corrections from 0.2 to 1.2 mm, based on location. The most-distorted areas are around air cavities, e.g. sinuses.ConclusionsThe phantom data show the validity of our fast distortion correction algorithm. Patient-specific data are acquired in <2 min and analyzed and available for planning in less than a minute.     

MRI-guided voxel-based automatic semi-quantification of dopamine transporter imaging

PurposeFunctional imaging with ¹²³I-FP-CIT SPECT suffers from poor spatial resolution resulting in partial-volume effect, which affects the subsequent semi-quantification. Definition of regions of interest for semi-quantification is further subject to user's experience and inter-observer variability. The aim of this work has been to develop an automatic method for definition of volumes of interest and partial-volume correction using patient-specific MRI and providing complete contrast recovery in striatal region.MethodThe method consists of spatial pre-processing (image segmentation and multi-modality registration), partial-volume correction (performed by region-based voxel-wise technique), and calculation of uptake indices in striatal structures. Anthropomorphic striatal phantom was used to optimize the method and to assess linearity, accuracy, and reproducibility. The method was tested on 58 patient datasets and compared with clinical assessment and BasGan software.ResultsThe method works automatically. The output is highly linear regarding changing striatal uptake. Complete contrast recovery is achieved using 6.5 mm FWHM. Accuracy is better than 0.15 in terms of RMSE between measured and true uptake indices. Reproducibility is better than 5% for normal uptake ratio. The method outperformed clinical assessment in all measures. With patient data, it provided results closer to BasGan (RMSE 0.9) than to clinical assessment (RMSE 1.9) and fairly correlated with both.ConclusionThe proposed method provides complete recovery of striatal contrast under given acquisition and reconstruction conditions. It reduces intra- and inter-observer variability, accurately defines volumes of interest, and effectively suppresses partial-volume effect. It can be reproduced using publicly available software.     

Determining a correction factor for aerial surveys of harbor seals in California

Counts of pinnipeds provide a minimal estimate of population size because some unknown proportion of individuals is in the water during surveys. We determined a correction factor (CF) for Pacific harbor seals (Phoca vitulina richardii) by estimating the proportion ashore of 180 seals tagged with flipper‐mounted radio tags throughout California. The mean proportions of tagged individuals ashore during four complete surveys in 2004 were not different between central and northern California (F= 1.85, P= 0.18) or between sexes (F= 0.57, P= 0.45), but a lesser proportion of weaners was ashore than subadults or adults (F= 7.97, P= 0.001), especially in northern California. The CF calculated for the statewide census of harbor seals was 1.65, using transmitters operating during the survey (n= 114). Using a mark‐recapture estimator for tag survival (phi) and the four telemetry surveys the mean CF for central and northern California was 1.54 ± 0.38 (95% CI). A CF for southern California of 2.86 was based on a single survey. Using the mean CF of 1.54 and a statewide count in 2009 we estimated 30,196 (95% CI = 22,745–37,647) harbor seals in California.