Biology subjects

Chen, L.

Publications and source records attributed to Chen, L..

At least 991 records · Page 55Linked to original sources

bioRxiv2018

Astroglial dysfunctions drive aberrant synaptogenesis in developing brain with lengthy general anesthesia

Lengthy use of general anesthetics (GAs) causes cognitive deficits in developing brain, which has raised significant clinical concerns such that FDA is warning on the use of GAs in children younger than 3 years. However, the molecular and cellular mechanisms for GAs-induced neurotoxicity remain largely unknown. Here we report that sevoflurane, a commonly used GA in pediatrics, causes compromised astrocyte morphogenesis, spatiotemporally correlated to the synaptic overgrowth with reduced synaptic function in developing cortex in a regional-, exposure-length- and age-specific manner. Sevoflurane disrupts astrocyte Ca2+ homeostasis both acutely and chronically, which leads to the down regulation of Ezrin, an actin-binding membrane protein, which we found is critically involved in astrocyte morphogenesis in vivo. Importantly, in normal developing brain, the genetic intervention of astrocyte morphogenesis is sufficient to produce the aberrant synaptic structure and function virtually identical to the ones induced by lengthy sevoflurane exposure. Our data uncover that astrocytes are unexpectedly central targets for GAs to exert toxic effects, and that astrocyte morphological integrity is crucial for synaptogenesis in the developing brain.

neuroscience↗

bioRxiv2018

ACME: Pan-specific peptide-MHC class I binding prediction through attention-based deep neural networks

Prediction of peptide binding to MHC molecules plays a vital role in the development of therapeutic vaccines for the treatment of cancer. Although numerous computational methods have been developed to this end, several challenges still remain in predicting peptide-MHC interactions. Many previous methods are allele-specific, training separate models for individual alleles and are thus unable to yield accurate predictions for those alleles with limited training data. Despite that there exist several pan-specific algorithms that train a common model for different alleles, they only adopt simple model structures that generally have limited performance in capturing the complex underlying patterns of peptide-MHC interactions. Here we present ACME (Attention-based Convolutional neural networks for MHC Epitope binding prediction), a new pan-specific algorithm to accurately predict the binding affinities between peptides and MHC class I molecules, even for those new alleles that are not seen in the training data. Extensive tests have demonstrated that ACME can significantly outperform other state-of-the-art prediction methods with an increase of the Pearson Correlation Coefficient by up to 23 percent. In addition, its ability to identify strong-binding peptides has been experimentally validated. Moreover, by integrating the convolutional neural network with attention mechanism, ACME is able to extract interpretable patterns that can provide useful and detailed insights into the binding preferences between peptides and their MHC partners. All these results have demonstrated that ACME can provide a powerful and practically useful tool for the studies of peptide-MHC class I interactions.

bioinformatics↗

bioRxiv2018

A missense mutation of Ip3r1 in Dp2 mice leads to short-term mydriasis and unfolded protein response in the iris constrictor muscles

Ip3r1 encodes an inositol 1,4,5-triphosphate-responsive calcium channel. Mutations in the Ip3r1 gene in humans may cause Gillespie syndrome (GS) typically presents as fixed dilated pupils in affected infants, which was referred to as iris hypoplasia. However, there is no report of mice with Ip3r1 heterozygous mutations showing dilated pupils. Here, we report a new Ip3r1 allele (dilated pupil 2; Dp2) with short-term dilated pupil phenotype derived from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. This allele carries a G5927A transition mutation, which is predicted to result in a C1976Y amino acid change in the open reading frame. Histology and pharmacological tests show that the dilated pupil phenotype is a mydriasis caused by the functional defect in the iris constrictor muscles in Dp2. The dilated pupil phenotype in Dp2 was referred to as mydriasis and excluding iris hypoplasia. IHC analysis revealed increased expression of BIP protein, the master regulator of unfolded protein response (UPR) signaling, in Dp2 mice that did not recover. Apart from the dilated pupil phenotype (mydriasis), there are no other abnormal phenotypes including Ip3r1-related ataxia that may be found. This study is the first report of an Ip3r1 mutation being associated with the mydriasis phenotype. Dp2 mice represent a valuable self-healing model that may be used to study the therapeutic approach for Ip3r1-related diseases or diseases caused by similar pathomechanisms.

genetics↗

bioRxiv2018

Destin: toolkit for single-cell analysis of chromatin accessibility

SummarySingle-cell assay of transposase-accessible chromatin followed by sequencing (scATAC-seq) is an emerging new technology for the study of gene regulation with single-cell resolution. The data from scATAC-seq are unique sparse, binary, and highly variable even within the same cell type. As such, neither methods developed for bulk ATAC-seq nor single-cell RNA-seq data are appropriate. Here, we present Destin, a bioinformatic and statistical framework for comprehensive scATAC-seq data analysis. Destin performs cell-type clustering via weighted principle component analysis, weighting accessible chromatin regions by existing genomic annotations and publicly available regulomic data sets. The weights and additional tuning parameters are determined via model-based likelihood. We evaluated the performance of Destin using downsampled bulk ATAC-seq data of purified samples and scATAC-seq data from seven diverse experiments. Compared to existing methods, Destin was shown to outperform across all data sets and platforms. For demonstration, we further applied Destin to 2,088 adult mouse forebrain cells and identified cell type-specific association of previously reported schizophrenia GWAS loci. AvailabilityDestin toolkit is freely available as an R package at https://github.com/urrutiag/destin. Contactyuchaoj@email.unc.edu.

bioinformatics↗

bioRxiv2018

A Whole-Genome Association Approach for Large-scaled Inter-species Trait

Genome wide association studies (GWAS) have provided an avenue for the association between common genetic variants and complex traits. However, using SNP as a genetic marker, GWAS has been confined to detect genetic basis traits only for within species but not for the large-scale inter-species traits. Here, we propose a practical statistical approach that is using kmer frequencies as the genetic markers to associate genetic variants with large scale inter-species traits. We applied this new approach to the trait of chromosome number in 96 mammalian proteomes, and we prioritized 130 genes including TP53 and BAD, of which 6 were candidate genes. These genes were proved to be associated with cellular reaction of DNA double-strand breaks caused by chromosome fission/fusion. Our study provides a new effective genomic strategy to perform association studies for large-scaled inter-species traits, using the chromosome number as a case. We hope this approach could provide exploration for broadly widely traits.

genomics↗

bioRxiv2018

Venom Isosolenopsin A Delivers Rapid Knockdown of Fire Ant Competitors

Fire ant venoms are composed of insecticidal alkaloids named solenopsins. Whilst species-specific differences are reported, little attention was given to caste-specific venom adaptations. The venom of fire ants queens has remained poorly studied. Founding queens must succeed in isolation in the field, where venom is bound to play a role against competitor species. The venoms of fire ant queens are strikingly similar across different species, in being mainly composed of the alkaloid isosolenopsin A, regardless of the chemical diversity of the worker caste. From assuming this pattern as the evolutionary result of stabilising trait selection, we hypothesise a shared mechanism explaining the conserved venom composition among the fire ant queens of different species. Here we report that fire ant queen venom and its major compounds are much quicker to neutralise competitor ants than the more diverse venoms of workers. Three representative competitor ant species sympatric with invasive fire ants were selected, exposed on the head to venoms from invasive fire ant workers and queens of two main invasive species, Solenopsis invicta and S. geminata. The venom diversity in the worker caste of these species represent extremes in the chemical diversity of fire ants. Queen venoms delivers quicker knockdown of rival foragers than worker venoms. The effects are traced back to synthetic solenopsins demonstrating solenopsin A analogues are particularly efficient as contact neurotoxins. The observed effects are comparable to nicotine. Overall the venoms of S. invicta seem more lethal than of S. geminata, regardless of knockdown speed. We believe these are fundamental aspects in the chemical ecology of the invasive ants which have been long overlooked, and emphasise on the need for further studies into the venom biology of founding queens.

zoology↗

bioRxiv2018

Unsupervised deconvolution of molecular heterogeneity uncovers novel signatures and glia-neuron ratio

Introduction Introduction Results Discussion Methods AUTHOR CONTRIBUTIONS Competing interests Appendix References While the two major types of cells in the brain are known to be glia and neuron, the true ratio of glia to neurons in the brain remains a mystery. One of recent studies using efficient cell counting method provides compelling evidence for 1:1 ratio on four whole human brains 1. The same study also reveals that the ratio of glia to neurons in the brain varies from one region to another, sometimes dramatically, e.g., 3.76:1 in the cerebral cortex versus 1:4.3 in the cerebellum 1,2. However, other scientists have argued that more rigorous studies are needed in which just about every known ...

bioinformatics↗

bioRxiv2018

Gating TrkB switch by methylglyoxal enables GLO1 as a target for depression

The endogenous metabolite methylglyoxal (MGO) has recently emerged as a potential mediator of psychiatric disorders, such as anxiety and depression, but its precise mechanism of action remains poorly understood. Here, we find that MGO concentrations are decreased in the prefrontal cortex and hippocampus in rats subjected to chronic stress, and low-dose MGO treatment remarkedly enhances resilience to stress and alleviates depression-like symptoms. This effect is achieved by MGOs promotion on the synaptic plasticity in prefrontal cortex and hippocampus. Both in vitro and in vivo experiments show that MGO provokes the dimerization and autophosphorylation of TrkB and the subsequent activation of downstream Akt/CREB signaling, which leads to a rapid and sustained expression of brain-derived neurotrophic factor (BDNF). We further demonstrate that MGO directly binds to the extracellular domain of TrkB, but not its intracellular domain. In addition, we also identify a natural product luteolin and its derivative lutD as potent inhibitors of Glyoxalase 1 and validate their antidepressant effects in chronic stress rat models. The antidepressant role of endogenous MGO provides a new basis for the understanding and therapeutic intervention design for stress-associated mental disorders.

neuroscience↗

bioRxiv2018

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

BackgroundPlacental protein expression plays a crucial biological role during normal and complicated pregnancies. We hypothesized that: (1) circulating pregnancy-associated, placenta-related protein levels throughout gestation reflect the uncomplicated, full-term temporal progression of human gestation, and effectively estimates gestational ages (GAs); (2) pregnancies with underlying placental pathology, such as preeclampsia (PE), are associated with disruptions in this GA estimation in early gestation; (3) malfunctions of this GA estimation can be employed to identify impending PE. In addition, to explore the underlying biology and PE etiology, we set to compare protein gestational patterns of human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms.\n\nMethodsSerum levels of circulating placenta-related proteins - leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)- were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 PE subjects with 61 samples). Linear multivariate analysis of the targeted serological protein levels was performed to estimate the normal GA. Logarithmic transformed mean-squared errors of GA estimations were used to identify impending PE. Then the human gestational protein patterns were compared to those in the pregnant HO-1 mice.\n\nResultsAn elastic net (EN)-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using the serum levels of the 6 proteins at various GAs from women with normal uncomplicated pregnancies (n = 10 for training and n = 6 for validation). In pregnancies complicated by PE (n = 14), the EN model was not (R2 = -0.17) associated with GA at sampling in PE. Statistically significant deviations from the normal GA EN model estimations were observed in PE-associated pregnancies between GAs of 16-30 weeks (P = 0.01). The EN model developed with 5 proteins (ELA excluded due to the lack of robustness of the mouse ELA essay) performed similarly on normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (human: R2 = 0.27) and mouse HO-1 Het (mouse: R2 = 0.30) pregnancies. LEP out performed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse gestations.\n\nConclusionsAs revealed in both human and mouse GA EN analyses, temporal serological placenta-related protein patterns are tightly regulated throughout normal human pregnancies and can be significantly disrupted in pathologic PE states. LEP changes earlier during gestation than the well-established late GA PE biomarkers (sFlt-1 and PlGF). Our HO-1 Het mouse analysis provides direct evidence of the causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model. Therefore, longitudinal analyses of pregnancy-related protein patterns in sera, may not only help in the exploration of underlying PE pathophysiology but also provide better clinical utility in PE assessment.

molecular biology↗

bioRxiv2018

The Lineage-Specific Transcription Factor CDX2 Navigates Dynamic Chromatin to Control Distinct Stages of Intestine Development

Lineage-restricted transcription factors, such as the intestine-specifying factor CDX2, often have dual requirements across developmental time. Embryonic-loss of CDX2 triggers homeotic transformation of intestinal fate, while adult-onset Cdx2-loss compromises critical physiological functions but preserves intestinal identity. It is unclear how such diverse requirements are executed across the developmental continuum. Using primary and engineered human tissues, mouse genetics, and a multi-omics approach, we demonstrate that divergent CDX2 loss-of-function phenotypes in embryonic versus adult intestines correspond to divergent CDX2 chromatin-binding profiles in embryonic versus adult stages. CDX2 binds and activates distinct target genes in developing versus adult mouse and human intestinal cells. We find that temporal shifts in chromatin accessibility correspond to these context-specific CDX2 activities. Thus, CDX2 is not sufficient to activate a mature intestinal program, but rather, CDX2 responds to its environment, targeting stage-specific genes to contribute to either intestinal patterning or maturity. This study provides insights into the mechanisms through which lineage-specific regulatory factors achieve divergent functions over developmental time.

developmental biology↗

bioRxiv2018

5-Hydroxymethylcytosines from Circulating Cell-free DNA as Diagnostic and Prognostic Markers for Hepatocellular Carcinoma

The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC), the second-most common cause of cancer deaths worldwide. We sought to develop a clinically convenient and minimally-invasive approach that can be deployed at scale for the sensitive, specific, and highly reliable diagnosis of HCC, and to evaluate the potential prognostic value of this approach. The study cohort comprised of 2,728 subjects, including HCC patients (n = 1,208), controls (n = 965) (572 healthy individuals and 393 patients with benign lesions), as well as patients with chronic hepatitis B infection (CHB) (n =291), liver cirrhosis (LC) (n = 110), and cholangiocarcinoma (CCC) (n = 154), was recruited from three major liver cancer hospitals in Shanghai, China, from July 2016 to November 2017. Circulating cell-free DNA (cfDNA) were collected from plasma samples from these individuals before surgery or any radical treatment. Applying our 5hmC-Seal technique, the summarized 5-hydroxymethylcytosine (5hmC) profiles in cfDNA were obtained. Molecular annotation analysis suggested that the profiled 5hmC loci in cfDNA were enriched with liver tissue-derived regulatory markers (e.g., H3K4me1). We showed that a weighted diagnostic score (wd-score) based on 117 genes detected using the summarized 5hmC profiles in cfDNA accurately distinguished HCC patients from controls (AUC = 95.1%; 95% CI, 93.6-96.5%) in the validation set, markedly outperformed -fetoprotein (AFP) with superior sensitivity. The wd-scores, which not only detected early BCLC stages (e.g., Stage 0: AUC = 96.2%; 95% CI,94.1-98.4%) and small tumors (e.g., < 2 cm: AUC = 95.7%; 95% CI: 93.6-97.7%), also showed high capacity for distinguishing HCC from non-cancer patients with CHB/LC (AUC = 80.2%; 95% CI, 75.8-84.6%). Moreover, the prognostic value of 5hmC markers in cfDNA was evaluated for HCC recurrence, showing that a weighted prognostic score (wp-score) based on 16 marker genes predicted the recurrence risk (HR = 6.67; 95% CI, 2.81-15.82, p < 0.0001) in 555 patients who have been followed up after surgery. In conclusion, we have developed and validated a robust 5hmC-based diagnostic model that can be applied routinely with clinically feasible amount of cfDNA (e.g., from ~2-5 mL of plasma). Applying this new approach in the clinic could significantly improve the clinical outcomes of HCC patients, for example by early detection of those patients with surgically resectable tumors or as a convenient disease surveillance tool for recurrence.

cancer biology↗

bioRxiv2018

Chemical composition of essential oil from Folium nelumbinis and its antioxidant activity

This study is aim to determine the chemical composition and antioxidant activity of the essential oil from lotus leaves. The different methods and solvents were selected to extract oils from lotus leaves. About 38 components were found by GC-MS analysis, representing as 12, 15-octadecatrienoic acid (34.99%), linoleic acid and hexadecanoic acid. TBARS value, AV value and IV value reflected the various physicochemical indexes and lipid properties of Folium nelumbinis oil. Furthermore, antioxidant activities of the leaf samples were examined by FRAP and DPPH assays. In all systems, twice methanol-decolorized and ultrasonic-assisted essential oil using hexane solvent exhibited a higher potential activitythan than that of other extracts (ethanol, ethyl acetate and petroleum ether). These results provide a clear picture of the essential oils of Folium nelumbinis and demonstrate that the lotus leaves oil has an huge potential as a kind of chemical additive for the food industry owing to the strong antioxidant capacity.

plant biology↗

bioRxiv2018

Gut Microbiota in male patients with chronic traumatic complete spinal cord injury

This study examined the diversity and structure of gut microbiota in healthy adults and chronic traumatic complete spinal cord injury (SCI) patients, documented neurogenic bowel management of SCI patients. The V3-V4 region of 16S rRNA gene from DNA of 91 fecal samples of 48 healthy and 43 diseased subjects was amplified and sequenced. There was difference in gut microbiota between healthy adult males and females. Neurogenic bowel dysfunction (NBD) was common in patients with chronic traumatic complete SCI, patients with quadriplegia have longer time to defecate than paraplegic patients, with higher NBD scores and heavier neurogenic bowel symptoms. Gut microbiota dysbiosis existed in SCI patients. The abundance of Veillonellaceae and Prevotellaceae increased while Bacteroidaceae and Bacteroides decreased in SCI group. The abundance of Bacteroidaceae, Bacteroides in quadriplegia group and Acidaminococcaceae, Blautia in paraplegia group were significant high than the health male group. Serum biomarkers GLU, HDL, CR and NBD symptoms defecation time, COURSE had significant correlation with microbial community structure. This study presents a comprehensive landscape of gut microbiota in adult male patients with chronic traumatic complete SCI and documents their neurogenic bowel management. The gut microbiota dysbiosis of SCI patients was correlation with serum biomarkers and NBD symptoms.\n\nIMPORTANCENeurogenic bowel dysfunction is a major physical and psychological problem in patients with spinal cord injury, which can seriously affect the quality life of them. Gut dysbiosis are highly likely to occur in spinal cord injury patients There are few studies on intestinal microecology after spinal cord injury, and the clinical studies are fewer. It is importance to document their neurogenic bowel management and present a landscape of gut microbiota in them. We found the gut microbiota dysbiosis of spinal cord injury patients was correlation with serum biomarkers and neurogenic bowel dysfunction symptoms. These results may have implications in the next study about metagenomics and precision treatment of neurogenic bowel dysfunction in spinal cord injury patients.

neuroscience↗

bioRxiv2018

Multiple isotopic models using various kinetic fractionation coefficients to estimate δ18O of leaf water

Investigation of{delta} 18O of leaf water may improve our understanding of the evapotranspiration partitioning and material exchange between the inside and outside of leaves. In this study,{delta} 18O of bulk leaf water ({delta}L,b) was estimated by both isotopic-steady-state (ISS) and non-steady-state (NSS) assumptions considering the Peclet effect. Specifically, we carefully modified kinetic fractionation coefficients (k). The results showed that the Peclet effect is required to predict{delta} L,b. On the diel time scale, both NSS assumption + Peclet effect (NSS + P) and ISS assumption + Peclet effect (ISS + P) using modified k (k-modified) for{delta} L,b showed a good agreement with observed{delta} L,b (p > 0.05). When using previously proposed k, however, both NSS + P and ISS + P were not reliable estimators of{delta} L,b (p < 0.05). On a longer time scale (days), estimates of daily mean{delta} L,b from ISS + P outperformed the estimates from NSS + P when using the same k values. Also, the employment of k-modified improved model performance in predicting daily mean{delta} L,b compared to the use of previously proposed k. Clearly, special care must be taken concerning k when using isotopic models to estimate{delta} L,b.\n\nHighlightFor hourly and daily mean data sets, the employment of modified kinetic fractionation coefficients significantly improved model performance for{delta} 18O of bulk leaf water.

ecology↗

bioRxiv2018

Perceptual inference employs intrinsic alpha frequency to resolve perceptual ambiguity

The brain uses its intrinsic dynamics to actively predict observed sensory inputs, especially under perceptual ambiguity. However, it remains unclear how this inference process is neurally implemented in biasing perception of ambiguous inputs towards the predicted percepts. Using electroencephalography and intracranial recordings, we first show that the alpha-band frequency defines a unified time window for perceptual grouping across both space and time: information segments, either spatially or temporally segregated, will be integrated if they fall within the same alpha cycle. Moreover, predictions employ this prior knowledge on intrinsic alpha frequency to shift perceptual inference towards the most possibly observed percepts. Multivariate decoding analysis showed that perceptual inference, based on variance in prestimulus alpha frequency (PAF), biases post-stimulus neural representations by inducing preactivation of the predicted percepts. fMRI results additionally showed that prestimulus activity and intrinsic organization status in the frontoparietal attentional network predict perceptual outcomes, probably by modulating occipitoparietal PAFs.

neuroscience↗

bioRxiv2018

Circular RNAs regulate cancer stem cells by FMRP against CCAR1 complex in hepatocellular carcinoma

Circular RNA (circRNA) possesses great pre-clinical diagnostic and therapeutic potentials in multiple cancers. However, the underlying correlation between circRNAs and cancer stem cells (CSCs) has not been reported. The absence of circZKSCAN1 endowed several malignant properties including cancer stemness and tightly correlated with worse overall and recurrence-free survival rate in HCC cells in vitro and in vivo. Bioinformatics analysis and RNA immunoprecipitation-sequencing (RIP-seq) results revealed that circZKSCAN1 exerted its inhibitive role by competitively binding FMRP, therefore, block the binding between FMRP and {beta}-catenin-binding protein-cell cycle and apoptosis regulator 1 (CCAR1) mRNA, and subsequently restraining the transcriptional activity of Wnt signaling. In addition, RNA-splicing protein Quaking 5 was found downregulated in HCC tissues and responsible for the reduction of circZKSCAN1. Collectively, this study revealed the mechanisms underlying the regulatory role of circZKSCAN1 in HCC CSCs and identified the newly discovered Qki5- circZKSCAN1-FMRP-CCAR1-Wnt signaling axis as a potentially important therapeutic target for HCC treatment.\n\nStatement of significanceO_LICircZKSCAN1, a novel negative regulator for cancer stem cells, was firstly identified with reverse correlation with HCC prognosis.\nC_LIO_LICircZKSCAN1 directly targets FMRP, and competitive binding with {beta}-catenin-binding protein cell cycle and apoptosis regulator 1 (CCAR1) for its activity.\nC_LIO_LIThe decreased expression of Quaking 5 is responsible for the absence of circZKSCAN1 in HCC.\nC_LI

cancer biology↗

bioRxiv2018

Mesenchymal stem cells protect retinal ganglion cells from degeneration via mitochondrial donation

Retinal ganglion cell (RGC) degeneration is extremely hard to repair or regenerate and is often coupled with mitochondrial dysfunction. Mesenchymal stem cells (MSCs)-based treatment has been demonstrated beneficial for RGC against degeneration. However, underlying mechanisms of MSC-provided RGC protection are largely unknown other than neuropectective paracrine actions. In this study, we sought to investigate whether mitochondrial donation can preserve RGC functions, in a mitochondrial Ndufs4 deficient mouse model of RGC degeneration. The results revealed intravitreal transplanted by induced pluripotent stem cell derived-MSCs (iPSC-MSC) could donate their mitochondria through crossing inner limited membrane to host RGCs. Furthermore, the donated mitochondria effectively protected against RGC death and largely preserved retinal function in Ndufs4-KO mice. Importantly, the protective effects of mitochondrial donation from MSCs were associated with management of pro-inflammatory cytokines. Our data identified a novel role of MSCs-mitochondrial donation in protection of RGC from degeneration, and highlight a viable therapeutic strategy by manipulating stem cell mitochondrial donation for the treatment of retina degeneration in future.

cell biology↗

bioRxiv2018

BAMM-SC: A Bayesian mixture model for clustering droplet-based single cell transcriptomic data from population studies

The recently developed droplet-based single cell transcriptome sequencing (scRNA-seq) technology makes it feasible to perform a population-scale scRNA-seq study, in which the transcriptome is measured for tens of thousands of single cells from multiple individuals. Despite the advances of many clustering methods, there are few tailored methods for population-scale scRNA-seq studies. Here, we have developed a BAyesiany Mixture Model for Single Cell sequencing (BAMM-SC) method to cluster scRNA-seq data from multiple individuals simultaneously. Specifically, BAMM-SC takes raw data as input and can account for data heterogeneity and batch effect among multiple individuals in a unified Bayesian hierarchical model framework. Results from extensive simulations and application of BAMM-SC to in-house scRNA-seq datasets using blood, lung and skin cells from humans or mice demonstrated that BAMM-SC outperformed existing clustering methods with improved clustering accuracy and reduced impact from batch effects. BAMM-SC has been implemented in a user-friendly R package with a detailed tutorial available on www.pitt.edu/~Cwec47/singlecell.html.

bioinformatics↗