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Biology subjects

Cao, Y.

Publications and source records attributed to Cao, Y..

At least 217 records · Page 12Linked to original sources

Robust prediction of patient outcomes with immune checkpoint blockade therapy for cancer using common clinical, pathologic, and genomic features

Despite the revolutionary impact of immune checkpoint blockade (ICB) in cancer treatment, accurately predicting patients responses remains elusive. We analyzed eight cohorts of 2881 ICB-treated patients across 18 solid tumor types, the largest dataset to date, examining diverse clinical, pathologic, and genomic features. We developed the LOgistic Regression-based Immunotherapy-response Score (LORIS) using a transparent, compact 6-feature logistic regression model. LORIS outperforms previous signatures in ICB response prediction and can identify responsive patients, even those with low tumor mutational burden or tumor PD-L1 expression. Importantly, LORIS consistently predicts both objective responses and short-term and long-term survival across most cancer types. Moreover, LORIS showcases a near-monotonic relationship with ICB response probability and patient survival, enabling more precise patient stratification across the board. As our method is accurate, interpretable, and only utilizes a few readily measurable features, we anticipate it will help improve clinical decision-making practices in precision medicine to maximize patient benefit.

cancer biology↗

Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease with currently no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in At-Risk populations prior to clinical disease onset is crucial to establishing effective prevention strategies. Here, we applied mass cytometry to deeply characterize the immunophenotypes in blood from At-Risk individuals identified through the presence of serum antibodies to citrullinated protein antigens (ACPA) and/or first-degree relative (FDR) status (n=52), as compared to established RA (n=67), and healthy controls (n=48). We identified significant cell expansions in At-Risk individuals compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5low naive B cell population was expanded in ACPA-positive FDRs. Further, we developed an "RA immunophenotype score" classification method based on the degree of enrichment of cell states relevant to established RA patients. This score significantly distinguished At-Risk individuals from controls. In all, we systematically identified activated lymphocyte phenotypes in At-Risk individuals, along with immunophenotypic differences among both ACPA+ and ACPA-FDR At-Risk subpopulations. Our classification model provides a promising approach for understanding RA pathogenesis with the goal to further improve prevention strategies and identify novel therapeutic targets.

genomics↗

Targeting Ribosome Biogenesis as a Novel Therapeutic Approach to Overcome EMT-related Chemoresistance in Breast Cancer.

Epithelial-to-mesenchymal transition (EMT) contributes significantly to chemotherapy resistance and remains a critical challenge in treating advanced breast cancer. The complexity of EMT, involving redundant pro-EMT signaling pathways and its paradox reversal process, mesenchymal-to-epithelial transition (MET), has hindered the development of effective treatments. In this study, we utilized a Tri-PyMT EMT lineage-tracing model and single-cell RNA sequencing (scRNA-seq) to comprehensively analyze the EMT status of tumor cells. Our findings revealed elevated ribosome biogenesis (RiBi) during the transitioning phases of both EMT and MET processes. RiBi and its subsequent nascent protein synthesis mediated by ERK and mTOR signalings are essential for EMT/MET completion. Importantly, inhibiting excessive RiBi genetically or pharmacologically impaired the EMT/MET capability of tumor cells. Combining RiBi inhibition with chemotherapy drugs synergistically reduced metastatic outgrowth of epithelial and mesenchymal tumor cells under chemotherapies. Our study suggests that targeting the RiBi pathway presents a promising strategy for treating patients with advanced breast cancer. SignificanceThis study uncovers the crucial involvement of ribosome biogenesis (RiBi) in the regulation of epithelial and mesenchymal state oscillations in breast cancer cells, which plays a major role in the development of chemoresistant metastasis. By proposing a novel therapeutic strategy targeting the RiBi pathway, the study offers significant potential to enhance treatment efficacy and outcomes for patients with advanced breast cancer. This approach could help overcome the limitations of current chemotherapy options and address the complex challenges posed by EMT-mediated chemoresistance.

cancer biology↗

Uncovering Ghost Introgression Through Genomic Analysis of a Distinct East Asian Hickory Species

Although the possibility of introgression from ghost lineages (all unsampled extant and extinct taxa) is now widely recognized, detecting and characterizing ghost introgression remains a challenge. Here, we propose a combined use of the popular D-statistic method, which tests for the presence of introgression, and the full-likelihood method BPP, which determines which of the possible gene-flow scenarios, including ghost introgression, is truly responsible. We illustrate the utility of this approach by investigating the reticulation and bifurcation history of the genus Carya (Juglandaceae), including the beaked hickory Carya sinensis. To achieve this goal, we generated two chromosome-level reference genomes respectively for C. sinensis and C. cathayensis. Furthermore, we re-sequenced the whole genomes of 43 individuals from C. sinensis and one individual from each of the 11 diploid species of Carya. The latter dataset with one individual per species is used to reconstruct the phylogenetic networks and estimate the divergence time of Carya. Our results unambiguously demonstrate the presence of ghost introgression from an extinct lineage into the beaked hickory, dispelling certain misconceptions about the phylogenetic history of C. sinensis. We also discuss the profound implications of ghost introgression into C. sinensis for the historical biogeography of hickory species. [BPP; Carya; D-statistic; gene flow; ghost introgression]

evolutionary biology↗

HSP90 inhibitor NVP-HSP990 alleviates rotavirus infection

Rotavirus (RV) infection is a significant cause of hospitalization and mortality in infants and young children. Although conventional symptomatic treatments usually appear effective, tens of thousands of infants and young children still die each year due to the absence of safe and effective anti-RV drugs. Heat shock protein 90 (HSP90) is usually required for efficient viral infection; however, due to unsatisfactory antiviral efficacy and toxicity, there has been no HSP90-targeting agents applied for clinical antiviral therapy currently. Here, we demonstrated that NVP-HSP990, a novel small-molecule HSP90 inhibitor with excellent oral bioavailability and brain penetration, was a potent inhibitor of RV infection with much bigger selectivity index (SI) than traditional HSP990 inhibitors. NVP-HSP990 potently inhibited RV replication in vitro without blocking infection establishment. NVP-HSP990 remarkably restored gene expressions of most KEGG pathways disturbed by RV infection in intestinal cells, except some inflammatory pathways (IL-17, TNF, etc.). To be noted, NVP-HSP990 significantly altered gene expressions in MAPK signaling pathway and inhibited RV-induced activation of MAPK as well as disruption of tight junctions in Caco-2 cells. More importantly, NVP-HSP990 effectively alleviated RV diarrhea, competently inhibited RV replication, and obviously prevented pathological lesions of intestine in BALB/c suckling mice. Therefore, our results suggested that NVP-HSP990 can be a promising antiviral drug candidate against RV infection.

microbiology↗

Structural polymorphisms within a common powdery mildew effector scaffold as a driver of co-evolution with cereal immune receptors

In plants, host-pathogen coevolution often manifests in reciprocal, adaptive genetic changes through variations in host nucleotide-binding leucine-rich repeat immune receptors (NLR) and virulence-promoting pathogen effectors. In grass powdery mildew (PM) fungi, an extreme expansion of a RNase-like effector family, termed RALPH, dominates the effector repertoire, with some members recognized as avirulence (AVR) effectors by cereal NLR receptors. We report the structures of the sequence-unrelated barley PM effectors AVRA6, AVRA7 and allelic AVRA10/AVRA22 variants, which are detected by highly sequence-related barley NLRs MLA6, MLA7, MLA10, and MLA22, and of wheat PM AVRPM2 detected by the unrelated wheat NLR PM2. The AVR effectors adopt a common scaffold, which is shared with the ribonuclease (RNase) T1/F1-family. We found striking variations in the number, position, and length of individual structural elements between RALPH AVRs, which is associated with a differentiation of RALPH effector subfamilies. We show that all RALPH AVRs tested have lost nuclease and synthetase activities of the RNase T1/F1- family and lack significant binding to RNA, implying that their virulence activities are associated with neo-functionalization events. Structure-guided mutagenesis identified six AVRA6 residues that are sufficient to turn a sequence-diverged member of the same RALPH subfamily into an effector specifically detected by MLA6. Similar structure-guided information for AVRA10 and AVRA22 indicates that MLA receptors detect largely distinct effector surface patches. Thus, coupling of sequence and structural polymorphisms within the RALPH scaffold of PMs facilitated escape from NLR recognition and potential acquisition of diverse virulence functions.

plant biology↗

Repeated Omicron infection alleviates SARS-CoV-2 immune imprinting

The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.51,2 and XBB.1.163,4, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters5-9. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who havent been exposed to Omicron yet should receive two updated vaccine boosters.

immunology↗

Tbx5 maintains atrial identity by regulating an atrial enhancer network

Understanding how the atrial and ventricular chambers of the heart maintain their distinct identity is a prerequisite for treating chamber-specific diseases. Here, we selectively inactivated the transcription factor Tbx5 in the atrial working myocardium of the neonatal mouse heart to show that it is required to maintain atrial identity. Atrial Tbx5 inactivation downregulated highly chamber specific genes such as Myl7 and Nppa, and conversely, increased the expression of ventricular identity genes including Myl2. Using combined single nucleus transcriptome and open chromatin profiling, we assessed genomic accessibility changes underlying the altered atrial identity expression program, identifying 1846 genomic loci with greater accessibility in control atrial cardiomyocytes compared to KO aCMs. 69% of the control-enriched ATAC regions were bound by TBX5, demonstrating a role for TBX5 in maintaining atrial genomic accessibility. These regions were associated with genes that had higher expression in control aCMs compared to KO aCMs, suggesting they act as TBX5-dependent enhancers. We tested this hypothesis by analyzing enhancer chromatin looping using HiChIP and found 510 chromatin loops that were sensitive to TBX5 dosage. Of the loops enriched in control aCMs, 73.7% contained anchors in control-enriched ATAC regions. Together, these data demonstrate a genomic role for TBX5 in maintaining the atrial gene expression program by binding to atrial enhancers and preserving tissue-specific chromatin architecture of atrial enhancers.

cell biology↗

Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previously suggested that an insufficient mucosal IgA response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot sufficiently boost the mucosal sIgA response in uninfected individuals, particularly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric and secretory IgA1 antibodies derived from four neutralizing IgG monoclonal antibodies targeting the receptor-binding domain of the spike protein (01A05, rmAb23, DXP-604 and XG014). Compared to their parental IgG antibodies, dimeric and secretory IgA1 antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgA1 form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2 and BA.4/5 with a 50-150-fold increase in potency, reaching the level of the most potent monoclonal antibodies described till date. In hACE2 transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Conversion of IgA and dimerization further enhanced or restored the neutralizing ability against the emerging Omicron sub-variants (DXP-604 for BQ.1, BQ.1.1 and BA2.75; 01A05 for BA2.75, BA.2.75.2 and XBB.1). Thus, dimeric or secretory IgA delivered by nasal administration may potentially be exploited for the treatment and prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by subvariants and, potentially, future VOCs. One Sentence SummaryEngineered dimeric and secretory IgA1 neutralized Omicron variant with higher potency than parental IgG.

microbiology↗

Early microbial intervention reduces diarrhea while improves later milk production in newborn calves

The rumen of neonatal calves is not well-developed and exhibits limited functionality. Therefore, the establishment of intestinal microbiota may play an instrumental role in their health and performance, but it has been rarely explored. Thus, we aim to explore the temporal colonization of the gut microbiome and the potential benefits of early microbial intervention in newborn calves. We followed up on the temporal dynamics of the gut microbiome and plasma metabolome in 36 newborn calves during the first two months of life and established their relationships with their health status and performance. We also evaluated whether microbiota transplantation (MT) could influence their phenotypes by modulating metabolism and its impact on later milk production performance.We showed that the composition and ecological interactions of the gut microbiome are likely to reach maturity one month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion, antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. The data from the study may help develop strategies to manipulate the gut microbiota during early life, which may be significantly relevant to the health and production of newborn calves. HIGHLIGHTSO_LIThe gut microbial composition and ecological interaction in newborn calves reach maturity one month after birth C_LIO_LITemporal shifts in the gut microbiome of newborn calves are associated with phenotypic changes, including growth, digestion, and antioxidative capacity C_LIO_LIEarly microbial intervention in newborn calves reduces diarrhea while improving later milk production C_LIO_LIThe gut microbial impact on newborn calves is mediated by plasma metabolites C_LI

microbiology↗

scBubbletree: quantitative visualization of single cell RNA-seq data

MotivationVisualization approaches transform high-dimensional data from single cell RNA sequencing (scRNA-seq) experiments into two-dimensional plots that are used for analysis of cell relationships, and as a means of reporting biological insights. Yet, many standard approaches generate visuals that suffer from overplotting, lack of quantitative information, and distort global and local properties of biological patterns relative to the original high-dimensional space. ResultsWe present scBubbletree, a new, scalable method for visualization of scRNA-seq data. The method identifies clusters of cells of similar transcriptomes and visualizes such clusters as "bubbles" at the tips of dendrograms (bubble trees), corresponding to quantitative summaries of cluster properties and relationships. scBubbletree stacks bubble trees with further cluster-associated information in a visually easily accessible way, thus facilitating quantitative assessment and biological interpretation of scRNA-seq data. Availability and Implementationthe R package scBubbletree is freely available at: https://bioconductor.org/packages/scBubbletree/ Contactsimo.kitanovski@uni-due.de, daniel.hoffmann@uni-due.de

bioinformatics↗

Microhomology-Mediated Circular DNA Formation from Oligonucleosomal Fragments During Spermatogenesis

The landscape of extrachromosomal circular DNA (eccDNA) during mammalian spermatogenesis, as well as the biogenesis mechanism remains to be explored. Here, we revealed widespread eccDNA formation in human sperms and mouse spermatogenesis. We noted that germline eccDNAs are derived from oligonucleosomal DNA fragmentation in cells likely undergoing cell death, providing a potential new way for quality assessment of human sperms. Interestingly, small-sized eccDNAs are associated with euchromatin, while large-sized ones are preferentially generated from heterochromatin. By comparing sperm eccDNAs with meiotic recombination hotspots and structural variations, we found that they are barely associated with de novo germline deletions. We further developed a bioinformatics pipeline to achieve nucleotide-resolution eccDNA detection even with the presence of microhomologous sequences that interfere with precise break-point identification. Empowered by our method, we provided strong evidence to show that microhomology-mediated end joining is the major eccDNA biogenesis mechanism. Together, our results shed lights on eccDNA biogenesis mechanism in mammalian germline cells.

genomics↗

Enhancer-promoter interactions are reconfigured through the formation of long-range multiway chromatin hubs as mouse ES cells exit pluripotency

Enhancers are genomic DNA sequences that bind transcription factors, chromatin regulators and non-coding transcripts to modulate the expression of target genes. They have been found to act from different locations relative to a gene and to modulate the activity of promoters up to [~]1 Mb away. Here we report the first 3D genome structures of single mouse ES cells as they are induced to exit pluripotency, transition through a formative stage and undergo neuroectodermal differentiation. In order to directly study how interactions between enhancers and promoters are reconfigured genome wide we have determined 3D structures of haploid cells using single cell Hi-C, where we can unambiguously map the contacts to particular chromosomes. We find that there is a remarkable reorganisation of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. Genes important for pluripotency exit establish contacts with emerging enhancers within multiway chromatin hubs as cells enter the formative state, consistent with these structural changes playing an important role in establishing new cell identities. Furthermore, we find that different multiway chromatin hubs, and thus different enhancer-promoter interactions, are formed in different individual cells. Our results suggest that studying genome structure in single cells will be important to identify key changes in enhancer-promoter interactions that occur as cells undergo developmental transitions.

developmental biology↗

Underlying driving forces of the SARS-CoV-2 evolution: immune evasion and ACE2 binding affinity

The evolution of SARS-CoV-2 is characterized by the emergence of new variants with a sheer number of mutations compared to their predecessors, which conferred resistance to pre-existing antibodies and/or increased transmissibility. The recently emerged Omicron subvariants also exhibit a strong tendency for immune evasion, suggesting adaptive evolution. However, previous studies have been limited to specific lineages or subsets of mutations, the overall evolutionary trajectory of SARS-CoV-2 and the underlying driving forces are still not fully understood. In this study, we analyzed the mutations present in all open-access SARS-CoV-2 genomes (until November 2022) and correlated the mutations incidence and fitness change with its impact on immune evasion and ACE2 binding affinity. Our results showed that the Omicron lineage had an accelerated mutation rate in the RBD region, while the mutation incidence in other genomic regions did not change dramatically over time. Moreover, mutations in the RBD region (but not in any other genomic regions) exhibited a lineage-specific pattern and tended to become more aggregated over time, and the mutation incidence was positively correlated with the strength of antibody pressure on the specific position. Additionally, the incidence of mutation was also positively correlated with changes in ACE2 binding affinity, but with a lower correlation coefficient than with immune evasion. In contrast, the mutations effect on fitness was more closely correlated with changes in ACE2 binding affinity than immune evasion. In conclusion, our results suggest that immune evasion and ACE2 binding affinity play significant and diverse roles in the evolution of SARS-CoV-2.

pathology↗

Predicting tumor immune microenvironment and checkpoint therapy response of head & neck cancer patients from blood immune single-cell transcriptomics

The immune state of tumor microenvironment is crucial for determining immunotherapy response but is not readily accessible. Here we investigate if we can infer the tumor immune state from the blood and further predict immunotherapy response. First, we analyze a dataset of head and neck squamous cell carcinoma (HNSCC) patients with matched scRNA-Seq of peripheral blood mononuclear cells (PBMCs) and tumor tissues. We find that the tumor immune cell fractions of different immune cell types and many of the genes they express can be inferred from the matched PBMC scRNA-Seq. Second, analyzing another HNSCC dataset with PBMC scRNA-Seq and immunotherapy response, we find that the inferred ratio between tumor memory B and regulatory T cell fractions is predictive of immunotherapy response and is superior to the well-established cytolytic and exhausted T-cell signatures. Overall, these results showcase the potential of scRNA-Seq liquid biopsies in cancer immunotherapy, calling for their larger-scale testing. SignificanceThis head and neck cancer study demonstrates the potential of using blood single-cell transcriptomics to (1) infer the tumor immune status and (2) predict immunotherapy response from the tumor immune status inferred from blood. These results showcase the potential of single-cell transcriptomics liquid biopsies for further advancing personalized cancer immunotherapy.

bioinformatics↗

Comparative analysis of chemical cross-linking mass spectrometry data indicates that protein STY residues rarely react with N-hydroxysuccinimide ester cross-linkers

Chemical cross-linking of proteins coupled with mass spectrometry (CXMS) has enjoyed growing popularity in biomedical research. Most CXMS experiments utilize cross-linkers based on N-hydroxysuccinimide (NHS) ester, which react selectively with the amine groups found on the free N-termini of proteins and on the side chain of lysine (K) residues. It is also reported that under certain conditions they can react with the hydroxyl groups of serine (S), threonine (T), and tyrosine (Y). Some of the popular cross-link search engines including MeroX and xiSearch set STY, in addition to K, as cross-linkable sites by default. However, to what extent NHS ester cross-linkers react with STY under the typical CXMS experimental conditions remains unclear, nor has the reliability of STY-cross-link identifications. Here, by setting amino acids with chemically inert side chains such as glycine (G), valine (V), and leucine (L) as cross-linkable sites, which serves as a negative control, we show that software-identified STY-cross-links are only as reliable as GVL-cross-links. This is true across different NHS ester cross-linkers including DSS, DSSO, and DSBU, and across different search engines including MeroX, xiSearch, and pLink. Using a published dataset originated from synthetic peptides, we demonstrate that STY-cross-links indeed have a high false discovery rate. Further analysis revealed that depending on the data and the CXMS search engine used to analyze the data, up to 65% of the STY-cross-links identified are actually K-K cross-links of the same peptide pairs, up to 61% are actually K-mono-links, and the rest tend to contain short peptides at high risk of false identification.

biochemistry↗

Benchmarking of analytical combinations for COVID-19 outcome prediction using single-cell RNA sequencing data

The advances of single-cell transcriptomic technologies have led to increasing use of single-cell RNA sequencing (scRNA-seq) data in large-scale patient cohort studies. The resulting high-dimensional data can be summarised and incorporated into patient outcome prediction models in several ways, however, there is a pressing need to understand the impact of analytical decisions on such model quality. In this study, we evaluate the impact of analytical choices on model choices, ensemble learning strategies and integration approaches on patient outcome prediction using five scRNA-seq COVID-19 datasets. First, we examine the difference in performance between using each single-view feature space versus multi-view feature space. Next, we survey multiple learning platforms from classical machine learning to modern deep learning methods. Lastly, we compare different integration approaches when combining datasets is necessary. Through benchmarking such analytical combinations, our study highlights the power of ensemble learning, consistency among different learning methods and robustness to dataset normalisation when using multiple datasets as the model input. Summary key pointsO_LIThis work assesses and compares the performance of three categories of workflow consisting of 350 analytical combinations for outcome prediction using multi-sample, multi-conditions single-cell studies. C_LIO_LIWe observed that using ensemble of feature types performs better than using individual feature type C_LIO_LIWe found that in the current data, all learning approaches including deep learning exhibit similar predictive performance. When combining multiple datasets as the input, our study found that integrating multiple datasets at the cell level performs similarly to simply concatenating the patient representation without modification. C_LI

bioinformatics↗

Multifaceted roles of a light-responsive factor LhWRKY44 in promoting anthocyanin accumulation in Asiatic hybrid lilies (Lilium spp.)

The coloration of Asiatic hybrid lily results mostly from anthocyanin accumulation in flowers. Although anthocyanin accumulation-related genes and MBW complexes are well studied, the transcriptional regulation of WRKY transcription factors involved in anthocyanin accumulation remains poorly understood.Here, we identified a lily WRKY protein, LhWRKY44, whose expression is highly expressed downstream of LhHY5 by light and positively correlated with anthocyanin accumulation. LhWRKY44 overexpression enhanced anthocyanin accumulation and silencing decreased anthocyanin accumulation in flowers. As a trans-acting regulator, LhWRKY44 activited the anthocyanin biosynthesis pathway-related genes PAL and F3H by binding to the their promoters. And the encoded TF also participates in anthocyanin transport and targets the intracellular anthocyanin transport protein GST promoters. Additionally, a novel dual activity of LhWRKY44 and LhMYBSPLATTER regulatory module, with LhWRKY44 binds to the promoter of LhMYBSPLATTER and interacts with LhMYBSPLATTER, strongly enhanced the interaction of LhMYBSPLATTER and LhbHLH2, indirectly enhancing DFR, UFGT and GST expression targeted by LhMYBSPLATTER. These results show a regulatory mode for light-induced anthocyanin accumulation enhancement by LhWRKY44 in lily, expanding our understanding of the complex transcriptional regulatory hierarchy modulating anthocyanin accumulation.

molecular biology↗