Integrated Analysis Research Articles

Integrative analysis of transcriptome and phytohormones reveals new genes network involved in shoot apical meristem development in maize under blue and red light

Blue and red light play a significant role in regulating transcriptional expression, phytohormone levels, and gene signal network reconstruction in the shoot apical meristem. To further elucidate the effects of red and blue light on transcriptional characteristics and phytohormone expression, and to explore signaling pathways and novel genes, we conducted comparative experiments under different light quality treatments. The results are as follows: a total of 22,327 genes were found to be effectively expressed, with a considerable number of alternative splicing events occurring concurrently. Furthermore, 1063 differentially expressed genes were identified, primarily associated with transcriptional variations resulting from the transition from blue light to red light. These differentially expressed genes are predominantly involved in KEGG annotations related to photosynthesis, DNA replication and carbon metabolism. The findings from targeted metabolism analysis reveal significant variations in 45 phytohormones, including ABA, auxin, CK, ETH, GA, JA, and SA. Correlation analysis between transcription and metabolism further indicates that IAA.Glc, IAA.Glu, TRP, mT9G, and GA53 show the strongest correlation with differentially expressed genes, with genes ssu1, ssu2, pep1, me3, and hsp90 displaying a significant relationship. Additionally, in the protein–protein interaction network, three novel genes (LOC100286132, LOC100510780, and LOC103653934) were identified as significant responding to the regulation of blue and red light. Following protein function analysis, the proteins were provisionally identified as ubiquitin conjugating enzyme-like, OXIDATIVE STRESS 3LIKE 2-like, and Ribosomal L 18p/L5e, respectively. Conclusively, it is depicted that the most significant impact of transitions between red light, blue light, and two light qualities lies in the transcriptional process of shot apical meristem of the C4 plant maize. This process is intricately linked to nitrogen availability, carbon dioxide assimilation capacity, and the stimulatory effects of auxin, cytokinin, and gibberellin. The expression of the putative L 18/L5e in blue and BTR light conditions may enhance transcript and synthesis capabilities of ribosome.

Proteogenomic insights into the biology and treatment of pan-melanoma

Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

Optimizing road safety: integrated analysis of motorized vehicle using lattice ordered complex linear diophantine fuzzy soft set

Optimizing road safety: integrated analysis of motorized vehicle using lattice ordered complex linear diophantine fuzzy soft set

Nanoliposomal irinotecan with fluorouracil and folinic acid, FOLFIRINOX, and S-1 as second-line treatment for unresectable pancreatic cancer after gemcitabine/nab-paclitaxel

This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab–paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.

Integrative analysis reveals the potential prognostic roles and immunological values of unc-5 netrin receptor A (UNC5A) in glioma

BackgroundUNC5A had been reported to play crucial roles in multiple cancers. However, little was known about the associations among UNC5A and glioma. Therefore, we first combined scRNA-seq, proteomics, as well as bulk RNA-seq in order to investigate UNC5A’s functions in gliomas.MethodsOnline databases provided scRNA-seq, proteomics, as well as bulk RNA-seq data on UNC5A in gliomas. The following procedures were conducted in order: QRT-PCR, Norman chart, gene set enrichment analysis (GSEA), and univariate/multifactor Cox regression analyses. We further explored the associations among UNC5A and tumor immunity.ResultsBy comparing gliomas with normal tissues, the TCGA dataset showed a significantly reduced expression of UNC5A, which was also confirmed by GSE50161, GSE4290, and QRT-PCR findings (p < 0.05). In both the TCGA and CGGA datasets, gliomas patients with low-UNC5A expression would have poorer overall survival (OS) prognoses (p < 0.05). ScRNA-seq analysis by the CancerSEA online website presented that UNC5A had a low expression in various glioma clusters and significantly associated with six functional states. Moreover, UNC5A might be a reliable independent biomarker of OS in gliomas patients (p < 0.05). Based on the results of GSEA, UNC5A might be connected to three significant pathways in gliomas. We also successfully created a Norman chart to assess the OS prognoses of these patients. Additionally, in aspects of tumor immunity, the infiltration levels of immune cells in LGG, the immune cell pathways, tumor immune microenvironment, as well as immune checkpoints in both LGG and GBM were revealed to be significantly influenced by UNC5A (p < 0.05).ConclusionsUNC5A was found to have prognostic and immunological significance in gliomas, offering patients with gliomas new treatment options.

RNA sequencing analysis of sexual dimorphism in Japanese quail

IntroductionJapanese quail are of significant economic value, providing protein nutrition to humans through their reproductive activity; however, sexual dimorphism in this species remains relatively unexplored compared with other model species.MethodA total of 114 RNA sequencing datasets (18 and 96 samples for quail and chicken, respectively) were collected from existing studies to gain a comprehensive understanding of sexual dimorphism in quail. Cross-species integrated analyses were performed with transcriptome data from evolutionarily close chickens to identify sex-biased genes in the embryonic, adult brain, and gonadal tissues.ResultsOur findings indicate that the expression patterns of genes involved in sex-determination mechanisms during embryonic development, as well as those of most sex-biased genes in the adult brain and gonads, are identical between quails and chickens. Similar to most birds with a ZW sex determination system, quails lacked global dosage compensation for the Z chromosome, resulting in directional outcomes that supported the hypothesis that sex is determined by the individual dosage of Z-chromosomal genes, including long non-coding RNAs located in the male hypermethylated region. Furthermore, genes, such as WNT4 and VIP, reversed their sex-biased patterns at different points in embryonic development and/or in different adult tissues, suggesting a potential hurdle in breeding and transgenic experiments involving avian sex-related traits.DiscussionThe findings of this study are expected to enhance our understanding of sexual dimorphism in birds and subsequently facilitate insights into the field of breeding and transgenesis of sex-related traits that economically benefit humans.

Relationships within Bolbitis sinensis Species Complex Using RAD Sequencing

Species identification and phylogenetic relationship clarification are fundamental goals in species delimitation. However, these tasks pose challenges when based on morphologies, geographic distribution, and genomic data. Previously, two species of the fern genus Bolbitis, B. × multipinna and B. longiaurita were described based on morphological traits; they are phylogenetically intertwined with B. sinensis and fail to form monophyletic groups. To address the unclear phylogenetic relationships within the B. sinensis species complex, RAD sequencing was performed on 65 individuals from five populations. Our integrated analysis of phylogenetic trees, neighbor nets, and genetic structures indicate that the B. sinensis species complex should not be considered as separate species. Moreover, our findings reveal differences in the degree of genetic differentiation among the five populations, ranging from low to moderate, which might be influenced by geographical distance and gene flow. The Fst values also confirmed that genetic differentiation intensifies with increasing geographic distance. Collectively, this study clarifies the complex phylogenetic relationships within the B. sinensis species complex, elucidates the genetic diversity and differentiation across the studied populations, and offers valuable genetic insights that contribute to the broader study of evolutionary relationships and population genetics within the Bolbitis species.

Epigenetic modification of PHLDA2 is associated with tumor microenvironment and unfavorable outcome of immune checkpoint inhibitor-based therapies in clear cell renal cell carcinoma

BackgroundA substantial proportion of patients with metastatic clear cell renal cell carcinoma (ccRCC) cannot derive benefit from immune checkpoint inhibitor (ICI) plus anti-angiogenic agent combination therapy, making identification of predictive biomarkers an urgent need. The members of pleckstrin homology-like domain family A (PHLDA) play critical roles in multiple cancers, whereas their roles in ccRCC remain unknown.MethodsTranscriptomic, clinical, genetic alteration and DNA methylation data were obtained for integrated analyses from TCGA database. RNA sequencing was performed on 117 primary tumors and 79 normal kidney tissues from our center. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis, gene set enrichment analysis were performed to explore transcriptomic features. Data from three randomized controlled trials (RCT), including CheckMate025, IMmotion151, JAVELIN101, were obtained for validation.ResultsMembers of PHLDA family were dysregulated in pan-cancer. Elevated PHLDA2 expression was associated with adverse clinicopathologic parameters and worse prognosis in ccRCC. Aberrant DNA hypomethylation contributed to up-regulation of PHLDA2. An immunosuppressive microenvironment featured by high infiltrates of Tregs and cancer-associated fibroblasts, was observed in ccRCC with higher PHLDA2 expression. Utilizing data from three RCTs, the association of elevated PHLDA2 expression with poor therapeutic efficacy of ICI plus anti-angiogenic combination therapy was confirmed.ConclusionsOur study revealed that elevated PHLDA2 expression regulated by DNA hypomethylation was correlated with poor prognosis and immunosuppressive microenvironment, and highlighted the role of PHLDA2 as a robust biomarker for predicting therapeutic efficacy of ICI plus anti-angiogenic agent combination therapy in ccRCC, which expand the dimension of precision medicine.

Tumor necrosis factor receptor 2 promotes endothelial cell-mediated suppression of CD8+ T cells through tuning glycolysis in chemoresistance of breast cancer

BackgroundT cells play a pivotal role in chemotherapy-triggered anti-tumor effects. Emerging evidence underscores the link between impaired anti-tumor immune responses and resistance to paclitaxel therapy in triple-negative breast cancer (TNBC). Tumor-related endothelial cells (ECs) have potential immunoregulatory activity. However, how ECs regulate T cell activity during TNBC chemotherapy remains poorly understood.MethodsSingle-cell analysis of ECs in patients with TNBC receiving paclitaxel therapy was performed using an accessible single-cell RNA sequencing (scRNA-seq) dataset to identify key EC subtypes and their immune characteristics. An integrated analysis of a tumor-bearing mouse model, immunofluorescence, and a spatial transcriptome dataset revealed the spatial relationship between ECs, especially Tumor necrosis factor receptor (TNFR) 2+ ECs, and CD8+ T cells. RNA sequencing, CD8+ T cell proliferation assays, flow cytometry, and bioinformatic analyses were performed to explore the immunosuppressive function of TNFR2 in ECs. The downstream metabolic mechanism of TNFR2 was further investigated using RNA sequencing, cellular glycolysis assays, and western blotting.ResultsIn this study, we identified an immunoregulatory EC subtype, characterized by enhanced TNFR2 expression in non-responders. By a mouse model of TNBC, we revealed a dynamic reduction in the proportion of the CD8+ T cell-contacting tumor vessels that could co-localize spatially with CD8+ T cells during chemotherapy and an increased expression of TNFR2 by ECs. TNFR2 suppresses glycolytic activity in ECs by activating NF-κB signaling in vitro. Tuning endothelial glycolysis enhances programmed death-ligand (PD-L) 1-dependent inhibitory capacity, thereby inducing CD8+ T cell suppression. In addition, TNFR2+ ECs showed a greater spatial affinity for exhausted CD8+ T cells than for non-exhausted CD8+ T cells. TNFR2 blockade restores impaired anti-tumor immunity in vivo, leading to the loss of PD-L1 expression by ECs and enhancement of CD8+ T cell infiltration into the tumors.ConclusionsThese findings reveal the suppression of CD8+ T cells by ECs in chemoresistance and indicate the critical role of TNFR2 in driving the immunosuppressive capacity of ECs via tuning glycolysis. Targeting endothelial TNFR2 may serve as a potent strategy for treating TNBC with paclitaxel.

Decoding the complex fluvial-lacustrine sedimentary interactions: Insights from the Neogene Guantao Formation in the Bohai Bay Basin and Modern Poyang Lake, China

Small-scale lake level variations lead to significant landward/basinward shifts in the depositional system, thereby facilitating the widespread development of fluvial-lacustrine interaction sedimentary systems. Such systems are commonly found in low-gradient shallow-water continental down-warped lacustrine basins, which are favorable for the formation of composite reservoir-caprock assemblages. Nevertheless, our understanding of the sedimentary stratigraphy of the Neogene Guantao Formation remains limited due to the complex and variable spatial and temporal associations between fluvial and lacustrine deposits. Integrated analysis of the geomorphology and stratigraphy of the modern Poyang Lake Basin and ancient Bohai Bay Basin (BBB) allows us to develop a process-based fluvial-lacustrine interaction model of shallow-water depositional system. Three physiographic zones are identified based on seasonal lake shoreline migration during a certain geological sequence unit, namely fluvial-dominated zone (FDZ), fluvial-lacustrine interaction zone (FLIZ) and lacustrine-dominated zone (LDZ), respectively. The FDZ is always above the maximum lake shoreline without affection by lake basin water body and is characterized by channelized dendritic pattern of distributary channels with positive rhythmic cycles. The FLIZ is a dynamic interaction region between the maximum lake shoreline and the lowest lake shoreline. Reticular distributary channels, delta front and prodelta/lake deposits vertically superimpose and dominate the system that is featured by complex sandbody, stacked positive and negative rhythms and strong water body segmentation. The LDZ, away from the fluvial effect, was identified below the lowest lake shoreline exhibiting polycentric sheet water body, dominated by lacustrine mudstone interspersed with thin sheet-like sandstone. These results shed light on the spatial and temporal sedimentary heterogeneity in such dynamic fluvial-lacustrine interaction systems. The proposed fluvial-lacustrine interaction model may serve as a valuable analogue for identifying sedimentary types and predicting sandstone reservoirs in similar shallow-water settings ranging from continental down-warped lacustrine basins to cratonic basins, and fault-depression basin gentle-slope belts.

Genomic and immune determinants of resistance to daratumumab-based therapy in relapsed refractory multiple myeloma

Targeted immunotherapy combinations, including the anti-CD38 monoclonal antibody (MoAb) daratumumab, have shown promising results in patients with relapsed/refractory multiple myeloma (RRMM), leading to a considerable increase in progression-free survival. However, a large fraction of patients inevitably relapse. To understand this, we investigated 32 relapsed MM patients treated with daratumumab, lenalidomide, and dexamethasone (Dara-Rd; NCT03848676). We conducted an integrated analysis using whole-genome sequencing (WGS) and flow cytometry in patients with RRMM. WGS before and after treatment pinpointed genomic drivers associated with early progression, including RPL5 loss, APOBEC mutagenesis, and gain of function structural variants involving MYC and chromothripsis. Flow cytometry on 202 blood samples, collected every 3 months until progression for 31 patients, revealed distinct immune changes significantly impacting clinical outcomes. Progressing patients exhibited significant depletion of CD38-positive NK cells, persistence of T-cell exhaustion, and reduced depletion of regulatory T cells over time. These findings underscore the influence of immune composition and daratumumab-induced immune changes in promoting MM resistance. Integrating genomics and flow cytometry unveiled associations between adverse genomic features and immune patterns. Overall, this study sheds light on the intricate interplay between genomic complexity and the immune microenvironment driving resistance to Dara-Rd in patients with RRMM.

Integrative analyses of metabolome and transcriptome reveal the dynamic accumulation and regulatory network in rhizomes and fruits of Polygonatum cyrtonema Hua

BackgroundAccording to Chinese ancient books, both fruits and rhizomes of Polygonatum cyrtonema Hua have medicinal and edible values. Up to now, there is no report about the metabolite profiles and regulatory network in fruits and different year-old rhizomes of P. cyrtonema.ResultsIn this study, we performed integrative analyses of metabolome and transcriptome to reveal the dynamic accumulation and regulatory network of fruits and different year-old rhizomes in P. cyrtonema. The relative content of phenolic acids, lignans and coumarins, flavonoids and alkaloids increased with growth years, while steroids and lipids decreased with it. In addition, the relative content of nucleotides and derivatives, flavonoids, organic acids, steroids and lipids in fruits were higher than rhizomes. Genes that might relate to the biosynthesis of polysaccharides, flavonoids, triterpene saponins and alkaloids biosynthesis were further analyzed by transcriptome analysis, including sacA, GMPP, PMM, CCoAOMT, CHI, ANR, CHS, DXS, GGPS, ZEP, CYP72A219 and so on, for their expressions were positively correlated with the relative content of the metabolites. Additionally, the correlation network in sugar and aromatic amino acids metabolites were constructed to further illustrate the biosynthesis of polysaccharides, flavonoids and alkaloids in P. cyrtonema, and some transcription factors (TFs) were screened, such as C2C2, MYB, bZIP, GRAS and NAC.ConclusionsThis study can deepen our understanding of the accumulation patterns and molecular mechanism of the main compounds in P. cyrtonema, and provide reference for the standardize production of P. cyrtonema.

Integrative analysis of gene and microRNA expression profiles reveals candidate biomarkers and regulatory networks in psoriasis.

Psoriasis (PS) is a chronic inflammatory skin disease with a long course and tendency to recur, the pathogenesis of which is not fully understood. This article aims to identify the key differentially expressed genes (DEGs) and microRNA (miRNAs) of PS, construct the core miRNA-mRNA regulatory network, and investigate the underlying molecular mechanism through integrated bioinformatics approaches. Two gene expression profile datasets and 2 miRNA expression profile datasets were downloaded from the gene expression omnibus (GEO) database and analyzed by GEO2R. Intersection DEGs and intersection differentially expressed miRNAs (DEMs) were each screened. The Metascape database and R software were used to perform enrichment analysis of intersecting DEGs and study their functions. Target genes of DEMs were predicted from the online database miRNet. The protein-protein interaction files of the overlapping target genes were obtained from string and the miRNA-mRNA network was constructed by Cytoscape software. In addition, the online web tool CIBERSORT was used to analyze the immune infiltration of dataset GSE166388, and the relative abundance of 22 immune cells in the diseased and normal control tissues was calculated and assessed. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the relative expression of the screened miRNAs and mRNAs to assess the applicability of DEMs and DEGs as biomarkers in PS. A total of 205 mating DEGs and 6 mating DEMs were screened. 103 dysregulated crossover genes from 205 crossover DEGs and 7878 miRNA target genes were identified. The miRNA-mRNA regulatory network was constructed and the top 10 elements were obtained from CytoHubba, including hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2. QRT-PCR revealed significant differences in miRNA and gene expression between inflammatory and normal states. In this study, the miRNA-mRNA core regulator pairs hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2 may be involved in the course of PS. This study provides new insights to discover new potential targets and biomarkers to further investigate the molecular mechanism of PS.

The Natural Infection of Freshwater Snails with the Avian Air Sac Fluke, Cyclocoelum mutabile (Trematoda: Cyclocoelidae), in Brazil

Trematodes of the family Cyclocoelidae are parasites mainly of the respiratory system of birds and present a cosmopolitan distribution. Although infection with these flukes can result in pathological changes and even bird death, information on their life cycles is scarce and almost entirely based on experimental infection data. Thus, the generation of knowledge on the mollusks that act as natural intermediate hosts of cyclocoelids is necessary and can aid control measures against these air sac trematodes. In the present study, gastropod mollusks collected in an urban stream from Belo Horizonte, Minas Gerais, Brazil, were subjected to the compression technique for the detection of non-emerging larval trematodes. Tailless cercariae with confluent ceca were found in 8/30 (26.7%) specimens of Biomphalaria glabrata and 3/33 (9.1%) specimen of Physella acuta. Samples of the cercariae were subjected to morphological characterization and genetic study (28S, Cox-1, and Nad-1). For comparative purposes, adult trematodes previously collected in the air sac of a common gallinule (Gallinula galeata) found dead in another waterbody from the same region were also characterized. The molecular sequences obtained revealed a high degree of similarity (100% in 28S, 99.2% in Cox-1, and 99.5% in Nad-1) between larval stages found in mollusks and adult parasites found in G. galeata and morphologically identified as Cyclocoelum mutabile. The conspecificity with this widely distributed cyclocoelid was also corroborated by phylogenetic analysis and comparison with isolates of this species previously characterized in Peru and the Czech Republic (99.4–100% and 96.7–97.0% of similarity in Nad-1, respectively). Thus, the integrative analysis carried out in the present work enabled us to identify C. mutabile in mollusks in South America for the first time. The finding of B. glabrata and P. acuta as new intermediate hosts corroborates the importance of freshwater gastropods in the transmission of C. mutabile, as well as the low specificity to the mollusk group, as previously characterized through experimental studies.

MIAMI-AD (Methylation in Aging and Methylation in AD): an integrative knowledgebase that facilitates explorations of DNA methylation across sex, aging, and Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder with a significant impact on aging populations. DNA methylation (DNAm) alterations have been implicated in both the aging processes and the development of AD. Given that AD affects more women than men, it is also important to explore DNAm changes that occur specifically in each sex. We created MIAMI-AD, a comprehensive knowledgebase containing manually curated summary statistics from 98 published tables in 38 studies, all of which included at least 100 participants. MIAMI-AD enables easy browsing, querying, and downloading DNAm associations at multiple levels-at individual CpG, gene, genomic regions, or genome-wide, in one or multiple studies. Moreover, it also offers tools to perform integrative analyses, such as comparing DNAm associations across different phenotypes or tissues, as well as interactive visualizations. Using several use case examples, we demonstrated that MIAMI-AD facilitates our understanding of age-associated CpGs in AD and the sex-specific roles of DNAm in AD. This open-access resource is freely available to the research community, and all the underlying data can be downloaded. MIAMI-AD facilitates integrative explorations to better understand the interplay between DNAm across aging, sex, and AD. Database URL: https://miami-ad.org/.

Integrative analysis of the transcriptome and proteome reveals the molecular responses of tobacco to boron deficiency

BackgroundBoron (B) is an essential micronutrient for plants. Inappropriate B supply detrimentally affects the productivity of numerous crops. Understanding of the molecular responses of plants to different B supply levels would be of significance in crop improvement and cultivation practices to deal with the problem.ResultsWe conducted a comprehensive analysis of the transcriptome and proteome of tobacco seedlings to investigate the expression changes of genes/proteins in response to different B supply levels, with a particular focus on B deficiency. The global gene and protein expression profiles revealed the potential mechanisms involved in the responses of tobacco to B deficiency, including up-regulation of the NIP5;1-BORs module, complex regulation of genes/proteins related to cell wall metabolism, and up-regulation of the antioxidant machinery.ConclusionOur results demonstrated that B deficiency caused severe morphological and physiological disorders in tobacco seedlings, and revealed dynamic expression changes of tobacco genes/proteins in response to different B supply levels, especially to B deficiency, thus offering valuable insights into the molecular responses of tobacco to B deficiency.

An integrated approach to analyzing matrix-crack-induced stiffness degradation and medium leakage in linerless composite vessels

This paper proposes an integrated analysis method for linerless composite vessels considering matrix-crack-induced stiffness degradation and permeation. Stiffness degradation models are obtained using machine learning regression, the data sets of which consist of finite element analysis (FEA) results and virtual samples. Then, the effective leakage conductance is obtained by using the linear elastic fracture mechanics and the micro-cracking leakage mechanism. The proposed integrated method is applied to analyze vessel structures designed by the grid theory, which has variable ply thicknesses and layup angles. Simulation results show that whether the structure at cryogenic temperature cracks and leaks more easily depends on its dimensions and stacking sequences.

Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology.

The Impact of Sparse Datasets When Harmonizing Data from Studies with Different Measures of the Same Construct.

Prevention science has increasingly turned to integrative data analysis (IDA) to combine individual participant-level data from multiple studies of the same topic, allowing us to evaluate overall effect size, test and model heterogeneity, and examine mediation. Studies included in IDA often use different measures for the same construct, leading to sparse datasets. We introduce a graph theory method for summarizing patterns of sparseness and use simulations to explore the impact of different patterns on measurement bias within three different measurement models: a single common factor, a hierarchical model, and a bifactor model. We simulated 1000 datasets with varying levels of sparseness and used Bayesian methods to estimate model parameters and evaluate bias. Results clarified that bias due to sparseness will depend on the strength of the general factor, the measurement model employed, and the level of indirect linkage among measures. We provide an example using a synthesis dataset that combined data on youth depression from 4146 youth who participated in 16 randomized field trials of prevention programs. Given that different synthesis datasets will embody different patterns of sparseness, we conclude by recommending that investigators use simulation methods to explore the potential for bias given the sparseness patterns they encounter.

Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM

BackgroudType II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets.MethodsRNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations.ResultsA total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition.ConclusionsIn summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.