Biology subjects

Fang, Q.

Publications and source records attributed to Fang, Q..

4 recordsLinked to original sources

bioRxiv2018

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↗

bioRxiv2018

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↗

bioRxiv2018

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↗

bioRxiv2017

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↗