ISMI-VAE: A deep learning model for classifying disease cells using gene expression and SNV data.

Various studies have linked several diseases, including cancer and COVID-19, to single nucleotide variations (SNV). Although single-cell RNA sequencing (scRNA-seq) technology can provide SNV and gene expression data, few studies have integrated and analyzed these multimodal data. To address this issue, we introduce Interpretable Single-cell Multimodal Data Integration Based on Variational Autoencoder (ISMI-VAE). ISMI-VAE leverages latent variable models that utilize the characteristics of SNV and gene expression data to overcome high noise levels and uses deep learning techniques to integrate multimodal information, map them to a low-dimensional space, and classify disease cells. Moreover, ISMI-VAE introduces an attention mechanism to reflect feature importance and analyze genetic features that could potentially cause disease. Experimental results on three cancer data sets and one COVID-19 data set demonstrate that ISMI-VAE surpasses the baseline method in terms of both effectiveness and interpretability and can effectively identify disease-causing gene features.

Blood pressure targets for acute ischemic stroke patients following endovascular thrombectomy: A meta-analysis.

OBJECTIVE: The objective of this meta-analysis was to explore the impact of different blood pressure levels following endovascular therapy on clinical outcomes, including safety and efficacy in acute ischemic stroke (AIS) patients. METHODS: A systematic search was performed on PubMed, Embase, Cochrane Library, and Web of Science databases, covering studies published before February 1, 2023. Our primary outcomes were 90-day mRs 0-2 score, 90-day mortality, incidence of symptomatic intracranial hemorrhage(sICH), and hemicraniectomy. RESULTS: The incidence of 90-day mRs= 2 score was no significant difference between different blood pressure values (OR=1.37, 95 % CI [0.82, 2.29], p = 0.23) with heterogeneity (I2 =85 %, p < 0.001). Subgroup analysis indicated that when the blood pressure targets were SBP< 140 mmHg (OR=1.73, 95 % CI [1.04, 2.90], p = 0.04) with heterogeneity (I2 =37 %, p = 0.20), and SBP< 130 mmHg (OR=1.58, 95 % CI [0.53, 4.70], p = 0.41) with heterogeneity (I2 =80 %, p = 0.02), there were statistic differences in the incidence of 90-day modified mRs 0-2 score. Regarding 90-day mortality, there was no significant difference between different blood pressure values (OR=0.75, 95 % CI [0.47, 1.21], p = 0.24; I2 =69 %, p = 0.007). As for the incidence of sICH, the difference was not statistically significant (OR = 0.82, 95 % CI [0.61, 1.09], p = 0.17; I2 =24 %, p = 0.26). However, subgroup analysis was performed due to different blood pressure values, and it was found that when the blood pressure targets were SBP＜140 mmHg (OR=0.49, 95 % CI [0.28, 0.87], p = 0.02) and SBP＜120 mmHg (OR = 0.84, 95 % CI [0.58, 1.23], p = 0.37), there were statistic differences in the incidence of sICH with SBP＜140 mmHg. Furthermore, SBP＜140 mmHg was associated with a lower incidence of hemicraniectomy (OR = 0.30, 95 % CI [0.15, 0.58], p＜0.001). PROSPERO Register Number: CRD42022376706 CONCLUSION: The present meta-analysis findings indicate that intensive treatment is advantageous for achieving successful reperfusion in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). For different blood pressure targets (SBP < 140mmhg, SBP < 130mmhg, SBP < 120mmhg), with a reduction in systolic blood pressure (SBP) to less than 140 mmHg appearing to confer the greatest benefit. Furthermore, this study provides a significant blood pressure target that could inform the design of future multicentre, open-label, blinded-endpoint, randomized controlled trials.

Identification of Key Ferroptosis-Related Genes in the Peripheral Blood of Patients with Relapsing-Remitting Multiple Sclerosis and Its Diagnostic Value.

Multiple sclerosis (MS) is a neurodegenerative disease with a complex pathogenesis. Re-lapsing-remitting multiple sclerosis (RRMS) is the most common subset of MS, accounting for approximately 85% of cases. Recent studies have shown that ferroptosis may contribute to the progression of RRMS, but the underlying mechanism remains to be elucidated. Herein, this study intended to explore the molecular network of ferroptosis associated with RRMS and establish a predictive model for efficacy diagnosis. Firstly, RRMS-related module genes were identified using weighted gene co-expression network analysis (WGCNA). Secondly, the optimal machine learning model was selected from four options: the generalized linear model (GLM), random forest model (RF), support vector machine model (SVM), and extreme gradient boosting model (XGB). Subsequently, the predictive efficacy of the diagnostic model was evaluated using receiver operator characteristic (ROC) analysis. Finally, a SVM diagnostic model based on five genes (JUN, TXNIP, NCOA4, EIF2AK4, PIK3CA) was established, and it demonstrated good predictive performance in the validation dataset. In summary, our study provides a systematic exploration of the complex relationship between ferroptosis and RRMS, which may contribute to a better understanding of the role of ferroptosis in the pathogenesis of RRMS and provide promising diagnostic strategies for RRMS patients.

Three amphioxus reference genomes reveal gene and chromosome evolution of chordates.

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.

Joint profiling of gene expression and chromatin accessibility during amphioxus development at single-cell resolution.

Vertebrate evolution was accompanied by two rounds of whole-genome duplication followed by functional divergence in terms of regulatory circuits and gene expression patterns. As a basal and slow-evolving chordate species, amphioxus is an ideal paradigm for exploring the origin and evolution of vertebrates. Single-cell sequencing has been widely used to construct the developmental cell atlas of several representative species of vertebrates (human, mouse, zebrafish, and frog) and tunicates (sea squirts). Here, we perform single-nucleus RNA sequencing (snRNA-seq) and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) for different stages of amphioxus (covering embryogenesis and adult tissues). With the datasets generated, we constructed a developmental tree for amphioxus cell fate commitment and lineage specification and characterize the underlying key regulators and genetic regulatory networks. The data are publicly available on the online platform AmphioxusAtlas.

The evolutionary origin and domestication history of goldfish (Carassius auratus).

Goldfish have been subjected to over 1,000 y of intensive domestication and selective breeding. In this report, we describe a high-quality goldfish genome (2n = 100), anchoring 95.75% of contigs into 50 pseudochromosomes. Comparative genomics enabled us to disentangle the two subgenomes that resulted from an ancient hybridization event. Resequencing 185 representative goldfish variants and 16 wild crucian carp revealed the origin of goldfish and identified genomic regions that have been shaped by selective sweeps linked to its domestication. Our comprehensive collection of goldfish varieties enabled us to associate genetic variations with a number of well-known anatomical features, including features that distinguish traditional goldfish clades. Additionally, we identified a tyrosine-protein kinase receptor as a candidate causal gene for the first well-known case of Mendelian inheritance in goldfish-the transparent mutant. The goldfish genome and diversity data offer unique resources to make goldfish a promising model for functional genomics, as well as domestication.

Chromosome genome assembly and annotation of the yellowbelly pufferfish with PacBio and Hi-C sequencing data.

Pufferfish are ideal models for vertebrate chromosome evolution studies. The yellowbelly pufferfish, Takifugu flavidus, is an important marine fish species in the aquaculture industry and ecology of East Asia. The chromosome assembly of the species could facilitate the study of chromosome evolution and functional gene mapping. To this end, 44, 27 and 50 Gb reads were generated for genome assembly using Illumina, PacBio and Hi-C sequencing technologies, respectively. More than 13 Gb full-length transcripts were sequenced on the PacBio platform. A 366 Mb genome was obtained with the contig of 4.4 Mb and scaffold N50 length of 15.7 Mb. 266 contigs were reliably assembled into 22 chromosomes, representing 95.9% of the total genome. A total of 29,416 protein-coding genes were predicted and 28,071 genes were functionally annotated. More than 97.7% of the BUSCO genes were successfully detected in the genome. The genome resource in this work will be used for the conservation and population genetics of the yellowbelly pufferfish, as well as in vertebrate chromosome evolution studies.