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Fang, Q.

Publications and source records attributed to Fang, Q..

62 records · Page 4Linked to original sources

GPU-accelerated mesh-based Monte Carlo photon transport simulations

The mesh-based Monte Carlo (MMC) algorithm is increasingly used as the gold-standard for developing new biophotonics modeling techniques in 3-D complex tissues, including both diffusion-based and various Monte Carlo (MC) based methods. Compared to multi-layered and voxel-based MCs, MMC can utilize tetrahedral meshes to gain improved anatomical accuracy, but also results in higher computational and memory demands. Previous attempts of accelerating MMC using graphics processing units (GPUs) have yielded limited performance improvement and are not publicly available. Here we report a highly efficient MMC - MMCL - using the OpenCL heterogeneous computing framework, and demonstrate a speedup ratio up to 420x compared to state-of-the-art single-threaded CPU simulations. The MMCL simulator supports almost all advanced features found in our widely disseminated MMC software, such as support for a dozen of complex source forms, wide-field detectors, boundary reflection, photon replay and storing a rich set of detected photon information. Furthermore, this tool supports a wide range of GPUs/CPUs across vendors and is freely available with full source codes and benchmark suites at http://mcx.space/#mmc.

bioengineering↗

Genome of an iconic Australian bird: Chromosome-scale assembly and linkage map of the superb fairy-wren (Malurus cyaneus)

The superb fairy-wren, Malurus cyaneus, is one of the most iconic Australian passerine species. This species belongs to an endemic Australasian clade, Meliphagides, which diversified early in the evolution of the oscine passerines. Today, the oscine passerines comprise almost half of all avian species diversity. Despite the rapid increase of available bird genome assemblies, this part of the avian tree has not yet been represented by a high-quality reference. To rectify that, we present the first chromosome-scale genome assembly of a Meliphagides representative: the superb fairy-wren. We combined Illumina shotgun and mate-pair sequences, PacBio long-reads, and a genetic linkage map from an intensively sampled pedigree of a wild population to generate this genome assembly. Of the final assembled 1.07Gb genome, 894Mb (84.8%) was anchored onto 25 chromosomes resulting in a final scaffold N50 of 68.11 Mb. This high-quality bird genome assembly is also one of only a handful which is also accompanied by a genetic map and recombination landscape. In comparison to other pedigree-based bird genetic maps, we find that the zebrafinch (Taeniopygia) genetic map more closely resembles the fairy-wren map rather than the map from the more closely-related Ficedula flycatcher. Lastly, we also provide a predictive gene and repeat annotation of the genome assembly. This new high quality, annotated genome assembly will be an invaluable resource not only to the superb fairy-wren species and relatives but also broadly across the avian tree by providing a new reference point for comparative genomic analyses.

genomics↗

Progressive alignment with Cactus: a multiple-genome aligner for the thousand-genome era

Cactus, a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequence. We describe progressive extensions to Cactus that enable reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We show that Cactus is capable of scaling to hundreds of genomes and beyond by describing results from an alignment of over 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment yet created. Further, we show improvements in orthology resolution leading to downstream improvements in annotation.

genomics↗

Mitochondrial DNA and their nuclear copies in parasitic wasp Pteromalus puparum: A comparative analysis in Chalcidoidea

Chalcidoidea (chalcidoid wasps) are an abundant and megadiverse insect group with both ecological and economical importance. Here we report a complete mitochondrial genome in Chalcidoidea from Pteromalus puparum (Pteromalidae). Eight tandem repeats followed by 6 reversed repeats were detected in its 3,308 bp control region. This long and complex control region may explain failures of amplifying and sequencing of complete mitochondrial genomes in some chalcidoids. In addition to 37 typical mitochondrial genes, an extra identical isoleucine tRNA (trnI) was detected. We speculate this recent mitochondrial gene duplication indicates that gene arrangements in chalcidoids are ongoing. A comparison among available chalcidoid mitochondrial genomes, reveals rapid gene order rearrangements overall, and high substitution rate in P. puparum. In addition, we identified 24 nuclear sequences of mitochondrial origin (NUMTs) in P. puparum, summing up to 9,989 bp, with 3,617 bp of these NUMTs originating from mitochondrial coding regions. NUMTs abundance in P. puparum is only one-twelfth of that in its relative, Nasonia vitripennis. Based on phylogenetic analysis, we provide evidence that a faster nuclear degradation rate contributes to the reduced NUMT numbers in P. puparum. Overall, our study shows unusually high rates of mitochondrial evolution and considerable variation in NUMT accumulation in Chalcidoidea.

genomics↗

Lead-DBS v2: Toward a comprehensive pipeline for deep brain stimulation imaging

Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural / functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patients preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the method of choice.\n\nThis work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field.

neuroscience↗

MethylSight: Taking a wider view of lysine methylation through computer-aided discovery to provide insight into the human methyl-lysine proteome

Protein Lys methylation plays a critical role in numerous cellular processes, yet it has been challenging to identify Lys methylation in a systematic manner. We present here an approach combining in silico prediction with targeted mass spectrometry (MS) to identify Lys methylation (Kme) sites at the proteome level. We have developed MethylSight, a program that predicts Kme events solely on physicochemical and biochemical properties of putative methylation sites, which can then be validated by targeted MS. Using this approach, we have identified 70 new histone Kme marks with a 90% validation rate. H2BK43me2, which undergoes dynamic changes during stem cell differentiation, is found to be a substrate of KDM5b. Furthermore, MethylSight predicts ~50,000 Kme sites in non-histone proteins with high confidence, suggesting that Lys methylation is a prevalent post-translational modification. Our work provides a useful resource for systematic exploration of the role of Lys methylation in human health and disease.

biochemistry↗

Mapping Human Hematopoietic Hierarchy At Single Cell Resolution By Microwell-seq

The classical hematopoietic hierarchy, which is mainly built with fluorescence-activated cell sorting (FACS) technology, proves to be inaccurate in recent studies. Single cell RNA-seq (scRNA-seq) analysis provides a solution to overcome the limit of FACS-based cell type definition system for the dissection of complex cellular hierarchy. However, large-scale scRNA-seq is constrained by the throughput and cost of traditional methods. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using extremely simple devices. Using Microwell-seq, we constructed a single-cell resolution transcriptome atlas of human hematopoietic differentiation hierarchy by profiling more than 50,000 single cells throughout adult human hematopoietic system. We found that adult human hematopoietic stem and progenitor cell (HSPC) compartment is dominated by progenitors primed with lineage specific regulators. Our analysis revealed differentiation pathways for each cell types, through which HSPCs directly progress to lineage biased progenitors before differentiation. We propose a revised adult human hematopoietic hierarchy independent of oligopotent progenitors. Our study also demonstrates the broad applicability of Microwell-seq technology.

cell biology↗