1. |
- Jin, Ying-Hui, et al.
(author)
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Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
- 2020
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In: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
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Journal article (peer-reviewed)abstract
- The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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2. |
- Yu, Wenjin, et al.
(author)
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Deep Learning-Based Classification of Cancer Cell in Leptomeningeal Metastasis on Cytomorphologic Features of Cerebrospinal Fluid
- 2022
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In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 1-11
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Journal article (peer-reviewed)abstract
- Background: It is a critical challenge to diagnose leptomeningeal metastasis (LM), given its technical difficulty and the lack of typical symptoms. The existing gold standard of diagnosing LM is to use positive cerebrospinal fluid (CSF) cytology, which consumes significantly more time to classify cells under a microscope.Objective: This study aims to establish a deep learning model to classify cancer cells in CSF, thus facilitating doctors to achieve an accurate and fast diagnosis of LM in an early stage.Method: The cerebrospinal fluid laboratory of Xijing Hospital provides 53,255 cells from 90 LM patients in the research. We used two deep convolutional neural networks (CNN) models to classify cells in the CSF. A five-way cell classification model (CNN1) consists of lymphocytes, monocytes, neutrophils, erythrocytes, and cancer cells. A four-way cancer cell classification model (CNN2) consists of lung cancer cells, gastric cancer cells, breast cancer cells, and pancreatic cancer cells. Here, the CNN models were constructed by Resnet-inception-V2. We evaluated the performance of the proposed models on two external datasets and compared them with the results from 42 doctors of various levels of experience in the human-machine tests. Furthermore, we develop a computer-aided diagnosis (CAD) software to generate cytology diagnosis reports in the research rapidly.Results: With respect to the validation set, the mean average precision (mAP) of CNN1 is over 95% and that of CNN2 is close to 80%. Hence, the proposed deep learning model effectively classifies cells in CSF to facilitate the screening of cancer cells. In the human-machine tests, the accuracy of CNN1 is similar to the results from experts, with higher accuracy than doctors in other levels. Moreover, the overall accuracy of CNN2 is 10% higher than that of experts, with a time consumption of only one-third of that consumed by an expert. Using the CAD software saves 90% working time of cytologists.Conclusion: A deep learning method has been developed to assist the LM diagnosis with high accuracy and low time consumption effectively. Thanks to labeled data and step-by-step training, our proposed method can successfully classify cancer cells in the CSF to assist LM diagnosis early. In addition, this unique research can predict cancer’s primary source of LM, which relies on cytomorphologic features without immunohistochemistry. Our results show that deep learning can be widely used in medical images to classify cerebrospinal fluid cells. For complex cancer classification tasks, the accuracy of the proposed method is significantly higher than that of specialist doctors, and its performance is better than that of junior doctors and interns. The application of CNNs and CAD software may ultimately aid in expediting the diagnosis and overcoming the shortage of experienced cytologists, thereby facilitating earlier treatment and improving the prognosis of LM.
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3. |
- Liu, Hui, et al.
(author)
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Centromere-Specific Retrotransposons and Very-Long-Chain Fatty Acid Biosynthesis in the Genome of Yellowhorn (Xanthoceras sorbifolium, Sapindaceae), an Oil-Producing Tree With Significant Drought Resistance
- 2021
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In: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 12
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Journal article (peer-reviewed)abstract
- In-depth genome characterization is still lacking for most of biofuel crops, especially for centromeres, which play a fundamental role during nuclear division and in the maintenance of genome stability. This study applied long-read sequencing technologies to assemble a highly contiguous genome for yellowhorn (Xanthoceras sorbifolium), an oil-producing tree, and conducted extensive comparative analyses to understand centromere structure and evolution, and fatty acid biosynthesis. We produced a reference-level genome of yellowhorn, ∼470 Mb in length with ∼95% of contigs anchored onto 15 chromosomes. Genome annotation identified 22,049 protein-coding genes and 65.7% of the genome sequence as repetitive elements. Long terminal repeat retrotransposons (LTR-RTs) account for ∼30% of the yellowhorn genome, which is maintained by a moderate birth rate and a low removal rate. We identified the centromeric regions on each chromosome and found enrichment of centromere-specific retrotransposons of LINE1 and Gypsy in these regions, which have evolved recently (∼0.7 MYA). We compared the genomes of three cultivars and found frequent inversions. We analyzed the transcriptomes from different tissues and identified the candidate genes involved in very-long-chain fatty acid biosynthesis and their expression profiles. Collinear block analysis showed that yellowhorn shared the gamma (γ) hexaploidy event with Vitis vinifera but did not undergo any further whole-genome duplication. This study provides excellent genomic resources for understanding centromere structure and evolution and for functional studies in this important oil-producing plant.
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5. |
- Cheng, Shi-Ping, et al.
(author)
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Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
- 2021
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In: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
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Journal article (peer-reviewed)abstract
- Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
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6. |
- Jia, Kai-Hua, et al.
(author)
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Chromosome-scale assembly and evolution of the tetraploid Salvia splendens (Lamiaceae) genome
- 2021
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In: Horticulture Research. - : Oxford University Press (OUP). - 2052-7276 .- 2662-6810. ; 8:1
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Journal article (peer-reviewed)abstract
- Polyploidization plays a key role in plant evolution, but the forces driving the fate of homoeologs in polyploid genomes, i.e., paralogs resulting from a whole-genome duplication (WGD) event, remain to be elucidated. Here, we present a chromosome-scale genome assembly of tetraploid scarlet sage (Salvia splendens), one of the most diverse ornamental plants. We found evidence for three WGD events following an older WGD event shared by most eudicots (the γ event). A comprehensive, spatiotemporal, genome-wide analysis of homoeologs from the most recent WGD unveiled expression asymmetries, which could be associated with genomic rearrangements, transposable element proximity discrepancies, coding sequence variation, selection pressure, and transcription factor binding site differences. The observed differences between homoeologs may reflect the first step toward sub- and/or neofunctionalization. This assembly provides a powerful tool for understanding WGD and gene and genome evolution and is useful in developing functional genomics and genetic engineering strategies for scarlet sage and other Lamiaceae species.
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7. |
- Li, Juan, et al.
(author)
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Unravelling the novel sex determination genotype with ‘ZY’ and a distinctive 2.15–2.95 Mb inversion among poplar species through haplotype-resolved genome assembly and comparative genomics analysis
- 2024
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In: Molecular Ecology Resources. - : John Wiley & Sons. - 1755-098X .- 1755-0998.
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Journal article (peer-reviewed)abstract
- Populus tomentosa, an indigenous tree species, is widely distributed and cultivated over 1,000,000 km2 in China, contributing significantly to forest production, ecological conservation and urban–rural greening. Although a reference genome is available for P. tomentosa, the intricate interspecific hybrid origins, chromosome structural variations (SVs) and sex determination mechanisms remain confusion and unclear due to its broad and even overlapping geographical distribution, extensive morphological variations and cross infiltration among white poplar species. We conducted a haplotype-resolved de novo assembly of P. tomentosa elite individual GM107, which comprises subgenomes a and b with a total genome size of 714.9 Mb. We then analysed the formation of hybrid species and the phylogenetic evolution and sex differentiation across the entire genus. Phylogenomic analyses suggested that GM107 likely originated from a hybridisation event between P. alba (♀) and P. davidiana (♂) approximately 3.8 Mya. A total of 1551 chromosome SVs were identified between the two subgenomes. More noteworthily, a distinctive inversion structure spanning 2.15–2.95 Mb was unveiled among Populus, Tacamahaca, Turaga, Aigeiros poplar species and Salix, highlighting a unique evolutionary feature. Intriguingly, a novel sex genotype of the ZY type, which represents a crossover between XY and ZW systems, was identified and confirmed through both natural and artificial hybrids populations. These novel insights offer significant theoretical value for the study of the species' evolutionary origins and serve as a valuable resource for ecological genetics and forest biotechnology.
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8. |
- Liu, Hui, et al.
(author)
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Repetitive elements, sequence turnover and cyto-nuclear gene transfer in gymnosperm mitogenomes
- 2022
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In: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
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Journal article (peer-reviewed)abstract
- Among the three genomes in plant cells, the mitochondrial genome (mitogenome) is the least studied due to complex recombination and intergenomic transfer. In gymnosperms only ∼20 mitogenomes have been released thus far, which hinders a systematic investigation into the tempo and mode of mitochondrial DNA evolution in seed plants. Here, we report the complete mitogenome sequence of Platycladus orientalis (Cupressaceae). This mitogenome is assembled as two circular-mapping chromosomes with a size of ∼2.6 Mb and which contains 32 protein-coding genes, three rRNA and seven tRNA genes, and 1,068 RNA editing sites. Repetitive sequences, including dispersed repeats, transposable elements (TEs), and tandem repeats, made up 23% of the genome. Comparative analyses with 17 other mitogenomes representing the five gymnosperm lineages revealed a 30-fold difference in genome size, 80-fold in repetitive content, and 230-fold in substitution rate. We found dispersed repeats are highly associated with mitogenome expansion (r = 0.99), and most of them were accumulated during recent duplication events. Syntenic blocks and shared sequences between mitogenomes decay rapidly with divergence time (r = 0.53), with the exceptions of Ginkgo and Cycads which retained conserved genome structure over long evolutionary time. Our phylogenetic analysis supports a sister group relationship of Cupressophytes and Gnetophytes; both groups are unique in that they lost 8–12 protein-coding genes, of which 4–7 intact genes are likely transferred to nucleus. These two clades also show accelerated and highly variable substitution rates relative to other gymnosperms. Our study highlights the dynamic and enigmatic evolution of gymnosperm mitogenomes.
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9. |
- Nie, Shuai, et al.
(author)
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Gapless genome assembly of azalea and multi-omics investigation into divergence between two species with distinct flower color
- 2023
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In: Horticulture Research. - : Oxford University Press. - 2662-6810 .- 2052-7276. ; 10:1
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Journal article (peer-reviewed)abstract
- The genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle. Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy, has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle, while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii. This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.
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10. |
- Shi, Tian-Le, et al.
(author)
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High-quality genome assembly enables prediction of allele-specific gene expression in hybrid poplar
- 2024
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In: Plant Physiology. - : Oxford University Press. - 0032-0889 .- 1532-2548. ; 195:1, s. 652-670
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Journal article (peer-reviewed)abstract
- Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid “84K” (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.
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