scEM: A New Ensemble Framework for Predicting Cell Type Composition Based on scRNA-Seq Data.

With the advent of single-cell RNA sequencing (scRNA-seq) technology, many scRNA-seq data have become available, providing an unprecedented opportunity to explore cellular composition and heterogeneity. Recently, many computational algorithms for predicting cell type composition have been developed, and these methods are typically evaluated on different datasets and performance metrics using diverse techniques. Consequently, the lack of comprehensive and standardized comparative analysis makes it difficult to gain a clear understanding of the strengths and weaknesses of these methods. To address this gap, we reviewed 20 cutting-edge unsupervised cell type identification methods and evaluated these methods comprehensively using 24 real scRNA-seq datasets of varying scales. In addition, we proposed a new ensemble cell-type identification method, named scEM, which learns the consensus similarity matrix by applying the entropy weight method to the four representative methods are selected. The Louvain algorithm is adopted to obtain the final classification of individual cells based on the consensus matrix. Extensive evaluation and comparison with 11 other similarity-based methods under real scRNA-seq datasets demonstrate that the newly developed ensemble algorithm scEM is effective in predicting cellular type composition.

Combining Global-Constrained Concept Factorization and a Regularized Gaussian Graphical Model for Clustering Single-Cell RNA-seq Data.

Single-cell RNA sequencing technology is one of the most cost-effective ways to uncover transcriptomic heterogeneity. With the rapid rise of this technology, enormous amounts of scRNA-seq data have been produced. Due to the high dimensionality, noise, sparsity and missing features of the available scRNA-seq data, accurately clustering the scRNA-seq data for downstream analysis is a significant challenge. Many computational methods have been designed to address this issue; nevertheless, the efficacy of the available methods is still inadequate. In addition, most similarity-based methods require a number of clusters as input, which is difficult to achieve in real applications. In this study, we developed a novel computational method for clustering scRNA-seq data by considering both global and local information, named GCFG. This method characterizes the global properties of data by applying concept factorization, and the regularized Gaussian graphical model is utilized to evaluate the local embedding relationship of data. To learn the cell-cell similarity matrix, we integrated the two components, and an iterative optimization algorithm was developed. The categorization of single cells is obtained by applying Louvain, a modularity-based community discovery algorithm, to the similarity matrix. The behavior of the GCFG approach is assessed on 14 real scRNA-seq datasets in terms of ACC and ARI, and comparison results with 17 other competitive methods suggest that GCFG is effective and robust.

Effect of aging in periocular appearances by comparison of anthropometry between early and middle adulthoods in Chinese Han population.

PURPOSE: Age-related change in ocular appearance occurs throughout adulthood, and involutional alterations in periocular tissues are common in middle-aged or older adults. This study sought to investigate significant differences in periocular anthropometry between young and middle-aged adults of Chinese Han ethnic group. METHODS: A total of 589 Chinese Han adults were recruited for cross-sectional investigation: 309 young adults (20 to 30 years), and 280 middle adulthood (50 to 70 years). Standardized, frontal view photographs were taken from each subject for measurements of 17 ocular anthropometric parameters (11 linear, three angular and three indicial parameters) detailing dimensions of palpebral fissures, and eyebrows. Eyelid crease morphologies were also evaluated. FINDINGS: Distribution of eyelid crease subtypes were different between the two age-groups, and an eyelid subtype (Type VI Closed Crescent) was uniquely found in middle-aged adults. Significant differences were found in majority of the ocular parameters. For most of the fissure-related measurements, values were greater in young adults. For some distance-dimensions between eyes and eyebrows, values were greater in the middle-aged adults. Detailed evaluation of periocular parameters of different age was individually performed for two subjects, which embodied findings from the cross-sectional analysis. CONCLUSIONS: By comparison of anthropometries between age-groups, we found alterations in periocular and eyelid morphologies under effect of aging, with association of laxity and loss of elasticity in periocular tissues. This study was the first to provide normative periocular dimensions of early and middle adulthoods in Chinese Han, which is useful for considerations in esthetic surgical decision-making for this population.

Anthropometric Analysis on the Ocular Region Morphology of Children and Young Adults in Chinese Han Population.

PURPOSE: The periocular features vary in different age groups and ethnic populations. In this study, the authors sought to determine whether age-related differences exist for certain periocular parameters between children and young adults of Chinese Han population. METHODS: OU of 310 children (aged 7-10 years) and 301 young adults (aged 20-30 years) were evaluated by 2-dimensional photogrammetry. All the subjects were of Chinese Han population. The eyelid crease profiles were classified according to their morphology. Periocular measurements, including 11 linear and 3 angular parameters were acquired from standardized photographs, 3 indices were further derived. The presence of epicanthal fold was also recorded. Each of the parameters was compared between the age groups. RESULTS: A statistical difference was found between the 2 age groups for the distribution of eyelid crease types. Statistical significances existed between the age groups for various parameters, these include palpebral fissure height and width, margin reflex distance, intercanthal and outercanthal width, distance from the medial end of the eyebrow to the medial canthus, distance from the lateral end of the brow to the lateral canthus, crease height and eyebrow height, angle of endocanthion and exocanthion, palpebral fissure inclination, palpebrae fissure index, canthal index, and angular index (p < 0.05). The incidence of epicanthal fold tended to decrease with increase of age. CONCLUSIONS: Age differences exist in periocular features between children and young adults of Chinese Han population. Standards of periocular measurements based on age and race could provide reliable guidelines for clinical examination and planning periocular surgery.

The inflammation influence on corneal surface after frontalis suspension surgery.

AIM: To study the influence of frontalis muscle flap suspension on ocular surface by analyzing the clinical features and inflammatory cytokines. METHODS: A prospective, observational case series. Thirty-one eyes of 25 patients with severe congenital blepharoptosis who underwent frontalis muscle flap suspension surgery with at least 6mo of follow-up were included in the study. The main outcome measures were margin reflex distance 1 (MRD1), degree of lagophthalmos, ocular surface disease index (OSDI), fluorescein staining (Fl), tear break-up time (BUT), Schirmer I test, and inflammatory cytokine assay. RESULTS: The degrees of lagophthalmos significantly increased after surgery. The OSDI scores significantly increased 1wk postoperatively and then decreased 4wk after operation. The Fl scores reflected corneal epithelial defects in sixteen patients at early stage postoperatively. The BUT and Schirmer I test values remained stable and did not show change compared to those before surgery. The inflammatory cytokines in conjunctival epithelial cells (including IL-1ß, IL-6, IL-8, TNF-α, and IL-17A) significantly increased 1wk after the surgery (P<0.001), then returned to the normal level at 24wk postoperatively. The levels of inflammatory cytokine IL-1ß, IL-6, IL-8, TNF-α, and IL-17A elevated significantly and were positively correlated with OSDI and Fl scores. CONCLUSION: Frontalis muscle flap suspension surgery results in lagophthalmos in early period of post-operation and relieved after months. The elevation of inflammatory cytokines level may participate in the occurrence of corneal epithelial defects at the early postoperative stage.

Tcf7l2 localization of putative stem/progenitor cells in mouse conjunctiva.

Conjunctival integrity and preservation is indispensable for vision. The self-renewing capacity of conjunctival cells controls conjunctival homeostasis and regeneration; however, the source of conjunctival self-renewal and the underlying mechanism is currently unclear. Here, we characterize the biochemical phenotype and proliferative potential of conjunctival epithelial cells in adult mouse by detecting proliferation-related signatures and conducting clonal analysis. Further, we show that transcription factor 7-like 2 (T-cell-specific transcription factor 4), a DNA binding protein expressed in multiple types of adult stem cells, is highly correlated with proliferative signatures in basal conjunctival epithelia. Clonal studies demonstrated that Transcription factor 7-like 2 (Tcf7l2) was coexpressed with p63α and proliferating cell nuclear antigen (PCNA) in propagative colonies. Furthermore, Tcf7l2 was actively transcribed concurrently with conjunctival epithelial proliferation in vitro. Collectively, we suggest that Tcf7l2 may be involved in maintenance of stem/progenitor cells properties of conjunctival epithelial stem/progenitor cells, and with the fornix as the optimal site to isolate highly proliferative conjunctival epithelial cells in adult mice.

Normative anthropometric analysis and aesthetic indication of the ocular region for young Chinese adults.

PURPOSE: The ocular region is of prime importance for the facial aesthetic outlook. Various anthropometric analyses for the periocular region have developed to ensure a pleasing postoperative appearance. However, little information exists for Chinese young adults. In this study, authors not only analyzed the periocular anthropometric characteristics, but, more importantly, searched out the most meaningful aesthetic indicators of the population. METHODS: The cross-sectional study was executed using two-dimensional photogrammetry acquired from 162 Chinese young adults (79 males, 83 females) between 20-30 years old. Anthropometric parameters including palpebral fissure length and height, intercanthal and outercanthal width, crease height, angle of endocanthion and exocanthion, axis of palpebral fissure, palpebral fissure index, canthal index, and angular index were acquired from standardized photographs. Then, 134 volunteers (20-30 years old) gave each photograph a score within 1-5 points to evaluate their ocular aesthetic attractiveness. The correlation between anthropometric parameters and aesthetic assessment was analyzed. RESULTS: A statistical difference between genders was found for palpebral fissure length and height, outercanthal width, angle of exocanthion, palpebral fissure index and canthal index (p < 0.05), with no statistical difference found for crease height between genders. Moreover, the palpebral fissure index, canthal index, crease height, and angle of exocanthion were significantly associated with aesthetic assessment. CONCLUSIONS: The normative anthropometric parameters are fundamental to interpret the morphology of eyes and to design plastic surgery for young Chinese adults. The parameters of palpebral fissure index, canthal index, crease height, and angle of exocanthion are strong indicators of aesthetic assessment.