Biology subjects

Wu, C.

Publications and source records attributed to Wu, C..

At least 109 records · Page 6Linked to original sources

bioRxiv2025

Asymmetric Histone Inheritance Regulates Differential Transcription Re-initiation and Cell Fate Decisions in Mouse Olfactory Horizontal Basal Cells

The olfactory epithelium (OE) possesses an adult stem cell population, the horizontal basal cells (HBCs), to permit lifelong tissue regeneration. Here we show that HBCs exhibit asymmetric inheritance of histone H4 but not H2A-H2B during OE regeneration in mice. Primary HBC cultures further revealed asymmetric histone inheritance for H3 and H3.3. Upon mitotic exit, asymmetric histone inheritance correlates with asynchronous transcription re-initiation and differential enrichment of p63, a key transcription factor for HBC cell fate. Disruption of asymmetric histone inheritance abolished these asymmetric cellular features and attenuated OE regeneration and smell behavior recovery. Single-cell RNA sequencing of paired HBC daughters in culture further supported asymmetric multilineage cell fate priming. Together, these findings reveal asymmetric histone inheritance in a mammalian adult stem cell lineage and highlight its biological significance in neural tissue regeneration and animal behavior.

developmental biology↗

bioRxiv2025

Single-cell omics-based characterization of human basophils reveals two transcriptionally distinct populations

BackgroundBasophils are implicated in various diseases including allergies, but a comprehensive characterization of human basophils has yet to be performed at the single-cell level. ObjectiveWe aimed to generate a single-cell omics-based resource of circulating human basophils, to be made accessible to the research community. We also sought to investigate basophil heterogeneity at the transcriptional and surface epitope levels. MethodsCirculating basophils were analyzed using short- and long-read single-cell RNA-sequencing in combination with large-scale immunoprofiling of more than 100 cell surface markers. ResultsWe used a cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) based cell barcoding system to accurately track side scatterlow lineage- CCR3+ Fc{varepsilon}RI+ basophils through the single-cell omics analysis. The approach allowed for accurate transcriptional profiling of basophils among low-density peripheral blood leukocytes. The generation of an additional dataset with only basophils revealed two transcriptionally distinct populations. Single-cell transcriptomic analysis of samples from additional donors was performed and coupled with a large-scale immunoprofiling screen, producing a third CITE-seq dataset containing basophils. The analysis verified the existence of the two transcriptionally distinct populations and revealed that these populations have similar immunophenotypes with regard to the investigated surface markers. Long-read single-cell RNA-sequencing analysis provided further insights into the gene expression dynamics of the circulating basophils and confirmed the transcriptionally defined basophil states. ConclusionsThe single-cell omics analysis revealed two transcriptionally distinct basophil populations. Our single-cell omics resource constitutes a reference for charting human basophils at the cellular and molecular levels in health and disease. Capsule summaryShort- and long-read single-cell RNA-sequencing coupled with large-scale immunoprofiling characterize human basophils in peripheral blood and reveal two transcriptionally distinct populations.

immunology↗

bioRxiv2025

POCALI: Prediction and insight On CAncer LncRNAs by Integrating multi-omics data with machine learning

Long non-coding RNAs (lncRNAs) are receiving increasing attention as biomarkers for cancer diagnosis and therapy. Although there are many computational methods to identify cancer lncRNAs, they do not comprehensively integrate multi-omics features for predictions or systematically evaluate the contribution of each omics to the multifaceted landscape of cancer lncRNAs. In this study, we developed an algorithm, POCALI, to identify cancer lncRNAs by integrating 44 omics features across six categories. We explored the contributions of different omics to identifying cancer lncRNAs and, more specifically, how each feature contributes to a single prediction. We also evaluated our model and benchmarked POCALI with existing methods. Finally, we validated the cancer phenotype and genomics characteristics of the predicted novel cancer lncRNAs. POCALI identified secondary structure and gene expression-related features as strong predictors of cancer lncRNAs, and epigenomic features as moderate predictors. POCALI performed better than other methods, especially in terms of sensitivity, and predicted more candidates. Novel POCALI-predicted cancer lncRNAs had strong relationships with cancer phenotypes, similar to known cancer lncRNAs. Overall, this study facilitated the identification of previously undetected cancer lncRNAs and the comprehensive exploration of the multifaceted feature contributions to cancer lncRNA prediction.

bioinformatics↗

bioRxiv2025

PROBind: A Web Server for Prediction, Analysis and Visualization of Protein-Protein and Protein-Nucleic Acid Binding Residues

Protein-protein and protein-nucleic acids interactions are fundamental to numerous cellular functions, yet only a small fraction have been experimentally characterized. Although modern computational methods have been developed for predicting interacting residues in proteins, they are challenging to use due to individual installation and execution requirements, lack of a standardized input or output format, and absence of support for result analysis. Moreover, methods trained using structures of complexes or intrinsically disordered regions, may not perform well on other types. To overcome these challenges, we develop PROBind, a web server for predicting, analyzing, and interactively visualizing protein, DNA and RNA binding residues from both protein sequences and structures. PROBind integrates 12 predictors trained on structural or disordered proteins, and supports the upload of results from external predictors. By normalizing and averaging predictions from multiple predictors targeting the same ligand type, PROBind generates meta-predictions that balance discrepancies among different methods. Furthermore, it provides interactive graphical tools for result analysis and contextualization. Overall, PROBind accommodates diverse ligand types and supports predictions and analysis based on both structure and sequence data, overcoming the limitations of existing tools. PROBind is freely accessible at https://www.csuligroup.com/PROBind.

bioinformatics↗

bioRxiv2025

Recurrent oncogenic ZC3H18 mutations stabilize endogenous retroviral RNA

Endogenous retroviral (ERV) RNA is highly expressed in cancer, although the molecular causes and consequences remain unknown. We found that ZC3H18 (Z18), a component of multiple nuclear RNA surveillance complexes, has recurrent truncating mutations in cancer. We show that Z18trunc mutations are oncogenic and that Z18 plays an evolutionarily conserved role in nuclear RNA surveillance of ERV RNA. In zebrafish, Z18trunc expedited melanoma onset and promoted a specific accumulation of ERV RNA. Z18 mutant human cell lines from the Cancer Cell Line Encyclopedia also expressed higher levels of ERV RNA. In engineered human melanoma cells, Z18trunc enhanced ERV RNA accumulation more than loss of one Z18 copy, indicating dominant negative activity. Z18trunc directly bound and stabilized ERV RNA. Notably, expression of ERV RNA was sufficient to expedite oncogenesis in a zebrafish model, which is the first evidence of which we are aware that ERV transcripts can play a functional role in cancer. Our work illuminates a mechanism for elevated ERV transcripts in cancer and supports that aberrant RNA accumulation is broadly oncogenic.

cancer biology↗

bioRxiv2025

Mitoxantrone inhibits and downregulates ERα through binding at the DBD-LBD interface

Targeting the estrogen receptor (ER or ER) through competitive antagonists, receptor downregulators, or estrogen synthesis inhibition remains the primary therapeutic strategy for luminal breast cancer. We have identified a novel mechanism of ER inhibition by targeting the critical interface between its DNA-binding domain (DBD) and ligand-binding domain (LBD). We demonstrate that mitoxantrone (MTO), a topoisomerase II inhibitor, binds at this previously unexplored DBD-LBD interface. Using comprehensive computational, biophysical, biochemical, and cellular analyses, we show that independent of its DNA damage response activity, MTO binding induces distinct conformational changes in ER, leading to its cytoplasmic redistribution and subsequent proteasomal degradation. Notably, MTO effectively inhibits clinically relevant ER mutations (Y537S and D538G) that confer resistance to current endocrine therapies, outperforming fulvestrant in both in vitro and in vivo assays. Our findings establish domain-domain interaction targeting as a viable therapeutic strategy for ER, with translational implications for other nuclear receptors.

cancer biology↗

bioRxiv2024

A continuation of the assembly of a G-quadruplex repair complex by the FANCJ DNA helicase

Guanine-rich nucleic acid sequences can adopt G-quadruplex (G4) structures, which pose barriers to DNA replication and repair. The FANCJ helicase contributes to genome stability by resolving these structures, a function linked to its G4-binding site that features an AKKQ amino acid motif. This site is thought to recognize oxidatively damaged G4, specifically those containing 8-oxoguanine (8oxoG) modifications. We hypothesize that FANCJ AKKQ recognition of 8oxoG-modified G4s (8oxoG4s) depends on the sequence context, the position of the lesion within the G4, and overall structural stability. Using fluorescence spectroscopy, we measured the binding affinities of a FANCJ AKKQ peptide for G4s formed by (GGGT)4, (GGGTT)4, and (TTAGGG)4 sequences. G4 conformation and thermal stability were assessed by circular dichroism spectroscopy. Each sequence was modified to include a single 8oxoG at the first (8oxo1), third (8oxo3), or fifth (8oxo5) guanine position. In potassium chloride (KCl), the most destabilized structures were (GGGT)4 8oxo1, (GGGTT)4 8oxo1, and (TTAGGG)4 8oxo5. In sodium chloride (NaCl), the most destabilized were (GGGT)4 8oxo1, (GGGTT)4 8oxo5, and (TTAGGG)4 8oxo5. FANCJ AKKQ binding affinities varied according to damage position and sequence context, with notable differences for (GGGT)4 in KCl and (TTAGGG)4 in NaCl. These findings support a model in which FANCJ binding to G4 and 8oxoG4 structures is modulated by both the oxidative damage position and the G4 local sequence environment.

biochemistry↗

bioRxiv2024

The CarSR Two-Component System Directly Controls radD Expression as a Global Regulator that Senses Bacterial Coaggregation in Fusobacterium nucleatum

Two-component systems (TCS) enable bacteria to sense and respond to environmental signals, facilitating rapid adaptation. Fusobacterium nucleatum, a key oral pathobiont, employs the CarSR TCS to modulate coaggregation with various Gram-positive partners by regulating the expression of radD, encoding a surface adhesion protein, as revealed by RNA-Seq analysis. However, the direct regulation of the radD-containing operon (radABCD) by the response regulator CarR, the broader CarR regulon, and the signals sensed by this system remain unclear. In this study, chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) identified approximately 161 CarR-enriched loci across the genome and a 17-bp consensus motif that likely serves as the CarR binding site. Notably, one such binding motif was found in the promoter region of the radABCD operon. The interaction of CarR with this binding motif was further validated using electrophoretic mobility shift assays (EMSA), mutagenesis, and DNase I footprinting analyses. Beyond regulating radABCD, CarR directly controls genes involved in fructose and amino acid (cysteine, glutamate, lysine) utilization, underscoring its role as a global regulator in F. nucleatum. Lastly, we discovered that RadD-mediated coaggregation enhances radD expression, and deletion of carS abolished this enhancement, suggesting that coaggregation itself serves as a signal sensed by this TCS. These findings provide new insights into the CarR regulon and the regulation of RadD, elucidating the ecological and pathogenic roles of F. nucleatum in dental plaque formation and disease processes. IMPORTANCEFusobacterium nucleatum is an essential member of oral biofilms, acting as a bridging organism that connects early and late colonizers, thus driving dental plaque formation. Its remarkable ability to aggregate with diverse bacterial partners is central to its ecological success, yet the mechanisms it senses and responds to these interactions remain poorly understood. This study identifies the CarSR two-component system as a direct regulator of RadD, the primary adhesin mediating coaggregation, and reveals its role in sensing coaggregation as a signal. These findings uncover a novel mechanism by which F. nucleatum dynamically adapts to polymicrobial environments, offering new perspectives on biofilm formation and bacterial communication in complex oral microbial ecosystems.

microbiology↗

bioRxiv2024

PlateletBase: A Comprehensive Knowledgebase for Platelet Research and Disease Insights

Platelets are vital in many pathophysiological processes, yet there is a lack of a comprehensive resource dedicated specifically to platelet research. To fill this gap, we have developed PlateletBase, a knowledge base aimed at enhancing the understanding and study of platelets and related diseases. Our team retrieved information from various public databases, specifically extracting and analyzing RNA-seq data from 3,711 samples across 41 different conditions available on NCBI. PlateletBase offers six analytical and visualization tools, enabling users to perform gene similarity analysis, pair correlation, multi-correlation, expression ranking, clinical information association, and gene annotation for platelets. The current version of PlateletBase includes 10,278 genomic entries, 31,758 transcriptomic entries, 4,869 proteomic entries, 2,614 omics knowledge entries, 1,833 drugs, 97 platelet resources, 438 diseases/traits, and six analysis modules. Each entry has been carefully curated and supported by experimental evidence. Additionally, PlateletBase features a user-friendly interface designed for efficient querying, manipulation, browsing, visualization, and analysis of detailed platelet protein and gene information. Case study results, such as those from gray platelet syndrome and angina pectoris, demonstrate that this tool can aid in identifying diagnostic biomarkers and exploring disease mechanisms, significantly advancing research in platelet functionality and its applications. PlateletBase is accessible at http://plateletbase.clinlabomics.org.cn/.

bioinformatics↗

bioRxiv2024

Employing Microsoft Sway as a Repository for Data Generated in Pharmaceutics Experimental Courses: A Case study on Topical Formulation Characterization

Microsoft Sway is an easy-to-use online creative software developed by Microsoft. It has many advantages as follows: easy to operate and does not require long-term practice and learning; network links can be created and accessed by devices such as Personal Computer (PC) and mobile terminals; Educators and Learners are allowed to browse this repository at anytime to facilitate the application prospects of mining relevant data. Therefore, the author proposes that Microsoft Sway may be a very promising data repository for pharmaceutical experimental teaching courses, and is expected to be extended to undergraduate experimental teaching in other natural science fields.

scientific communication and education↗

bioRxiv2024

Upregulating ANKHD1 in PS19 mice reduces Tau phosphorylation and mitigates Tau-toxicity-induced cognitive deficits

Abnormal accumulation of Tau protein in the brain disrupts normal cellular function and leads to neuronal death linked with many neurodegenerative disorders such as Alzheimers disease. An attractive approach to mitigate Tau-induced neurodegeneration is to enhance the clearance of toxic Tau aggregates. We previously showed that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration in fly disease models. Here we have generated a transgenic mouse line carrying Cre-inducible ANKHD1, the mouse homolog of mask, to determine whether the protective role of mask is conserved from flies to mammals. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we observed that ANKHD1 significantly reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, there was a notable trend towards reduced gliosis levels in these mice, suggesting a protective role of ANKHD1 against TauP301S-linked degeneration. Further analysis of 9-month- old mice revealed a similar trend of effects. Moreover, we found that ANKHD1 also suppresses the cognitive defect of 9-month-old PS19 female mice in novel object recognition (NOR) behavioral assay. Unlike previous therapeutic strategies that primarily focus on inhibiting Tau phosphorylation or directly clearing aggregates, this study highlights the novel role of ANKHD1 in promoting autophagy as a means to mitigate Tau pathology. This novel mechanism not only underscores ANKHD1s potential as a unique therapeutic target for tauopathies but also provides new insights into autophagy-based interventions for neurodegenerative diseases.

neuroscience↗

bioRxiv2024

A multi-tissue developmental gene expression atlas towards understanding the biological basis of phenotypes in sheep

Sheep (Ovis aries) represents one of the most important livestock species for animal protein and wool production worldwide. However, little is known about the genetic and biological basis of ovine phenotypes, particularly for those of high economic value and environmental impact. Here, by generating and integrating 1,413 RNA-seq samples from 51 distinct tissues across 14 developmental time points, representing early prenatal, late prenatal, neonate, lamb, juvenile, adult, and elderly stages, we built a high-resolution developmental Gene Expression Atlas (dGEA) in sheep. We observed dynamic patterns of gene expression and regulatory networks across tissues and developmental stages. When harnessing this resource for interpreting genomic associations of 48 monogenetic and 12 complex traits in sheep, we found that genes upregulated at prenatal developmental stages played more important roles in shaping these phenotypes than those upregulated at postnatal stages. For instance, genetic associations of crimp number, mean staple length (MSL), and individual birth weight were significantly enriched in the prenatal rather than postnatal skin and immune tissues. By comprehensively integrating fine-mapping results and the sheep dGEA, we identified several key genes associated with complex traits in sheep, such as SOX9 (associated with MSL), GNRHR (associated with litter size at birth), and PRKDC (associated with live weight). These results provide novel insights into the gene regulatory and developmental architecture underlying ovine phenotypes. The dGEA (https://sheepdgea.njau.edu.cn/) will serve as an invaluable resource for sheep developmental biology, genetics, genomics, and selective breeding.

genetics↗

bioRxiv2024

Multi-modal profiling identifies CD4+CXCR5+PD-1- Tfh cells as prognostic and predictive biomarkers for response to R-CHOP therapy in human DLBCL

Despite the improvements in clinical outcomes for patients with Diffuse Large B-Cell Lymphoma (DLBCL), a significant proportion of those patients still face challenges with refractory/relapsed (R/R) disease after receiving first-line R-CHOP treatment. Characterizing the heterogeneity of the tumor microenvironment (TME) in diffuse large B cell lymphoma (DLBCL) is crucial for understanding relapsed/refractory disease. However, the complex and diverse nature of the TME has impeded progress. Here, using single-cell RNA sequencing(scRNA-seq), we explored the DLBCL landscape at single-cell resolution, profiling 77,344 cells from both primary and relapsed DLBCL patients. We further investigated the shared and distinct molecular and cellular features of tumor microenvironment in both primary and relapsed DLBCL tumors by integrating next-generation DNA sequencing data and multiple scRNA-seq datasets from total 72,351 cells. Our results demonstrated that there was a significant decrease of CD4+CXCR5+PD-1- Tfh cells, along with excessive activation of the TNF-NF{kappa}B signaling pathways in malignant B cells in R/R disease. Furthermore, by using multiplex IHC, we confirmed that CD4+CXCR5+PD-1- Tfh cells are prognostic and predictive biomarkers for response to R-CHOP treatment. As a proof of concept, we successfully generated mutilplexed images of CD4+CXCR5+PD-1- Tfh cells from a single DAPI staining in human DLBCL tissues through using generative artificial intelligence. Our study offers critical insights into the heterogeneity and molecular features of DLBCL, shedding light on the crucial role of CD4+CXCR5+PD-1- Tfh cells in the recurrent process. HighlightsO_LIShared and distinct molecular and cellular features of tumor microenvironment in both primary and relapsed DLBCL tumors; C_LIO_LIThe characteristic of relapsed DLBCL TME is a dysfunctional immune microenvironment with a significant decrease of CD4+CXCR5+PD-1- Tfh cells. C_LIO_LICD4+CXCR5+PD-1- Tfh cells are prognostic and predictive biomarkers for response to R-CHOP treatment C_LIO_LIDetermination of CD4+CXCR5+PD-1- Tfh cells in human DLBCL tissues through using generative artificial intelligence. C_LI

immunology↗

bioRxiv2024

Structural Insights into Selective and Dual Antagonism of EP2 and EP4 Prostaglandin Receptors

Prostaglandin E2 (PGE2) signaling through EP2 and EP4 receptors plays a crucial role in inflammation, pain, and cancer progression. Selective and dual antagonists of these receptors have shown promising therapeutic potential. However, the structural basis for their binding modes and selectivity remained unclear. Here, we present cryo-EM structures of human EP2 and EP4 receptors in complex with selective antagonists PF-04418948 and grapiprant, respectively, as well as the dual antagonist TG6-129. These structures reveal distinct binding pockets and interaction networks that govern antagonist selectivity and efficacy. Combining the structural data and functional studies, we uncover the key residues and structural features that differentiate EP2 and EP4 binding sites, including a unique {pi}-{pi} stacking interaction in EP2 and variations in pocket shape and charge distribution. The dual antagonist TG6-129 exhibited a novel binding mode, interacting deeply with EP2 but only shallowly with EP4 in a two-warhead manner. These findings provide a structural framework for understanding prostanoid receptor pharmacology and offer valuable insights for the rational design of improved selective and dual antagonists targeting EP2 and EP4 receptors.

biochemistry↗

bioRxiv2024

Structural insights into HIV-2 CA lattice formation and FG-pocket binding revealed by single particle cryo-EM.

One of the most striking features of HIV is the capsid; a fullerene cone comprised of the pleomorphic capsid protein (CA) which shields the viral genome from cellular defense mechanisms and recruits cellular cofactors to the virus. Despite significant advances in understanding the mechanisms of HIV-1 CA assembly and host factor interaction, HIV-2 CA remains poorly understood. By templating the assembly of HIV-2 CA on functionalized liposomes, we were able to determine high resolution structures of the HIV-2 CA lattice, including both CA hexamers and pentamers, alone and in complexes with peptides of host phenylalanine-glycine (FG)-motif proteins Nup153 and CPSF6. While the overall fold and mode of binding the FG-peptides are conserved with HIV-1, this study reveals distinctive structural features that define the HIV-2 CA lattice, potential differences in interactions with other host factors such as CypA, and divergence in the mechanism of formation of hexameric and pentameric CA assemblies. This study extends our understanding of HIV capsids and highlights an approach with significant potential to facilitate the study of lentiviral capsid biology.

biochemistry↗

bioRxiv2024

Structural insights into inhibitor mechanisms on immature HIV-1 Gag lattice revealed by high-resolution in situ single-particle cryo-EM

HIV-1 inhibitors, such as Bevirimat (BVM) and Lenacapavir (LEN), block the production and maturation of infectious virions. However, their mechanisms remain unclear due to the absence of high-resolution structures for BVM complexes and LENs structural data being limited to the mature capsid. Utilizing perforated virus-like particles (VLPs) produced from mammalian cells, we developed an approach to determine in situ cryo-electron microscopy (cryo-EM) structures of HIV-1 with inhibitors. This allowed for the first structural determination of the native immature HIV-1 particle with BVM and LEN bound inside the VLPs at high resolutions. Our findings offer a more accurate model of BVM engaging the Gag lattice and, importantly, demonstrate that LEN not only binds the mature capsid but also targets the immature lattice in a distinct manner. The binding of LEN induces a conformational change in the capsid protein (CA) region and alters the architecture of the Gag lattice, which may affect the maturation process. These insights expand our understanding of the inhibitory mechanisms of BVM and LEN on HIV-1 and provide valuable clues for the design of future inhibitors.

biochemistry↗

bioRxiv2024

MirGeneDB 3.0: Improved taxonomic sampling, uniform nomenclature of novel conserved microRNA families, and updated covariance models.

We present a major update of MirGeneDB (3.0), the manually curated animal microRNA gene database. Beyond moving to a new server and the creation of a computational mirror, we have expanded the database with the addition of 33 invertebrate species, including representatives of 5 previously unsampled phyla, and 6 mammal species. MirGeneDB now contains entries for 21, 822 microRNA genes (5, 160 of these from the new species) belonging to 1743 microRNA families. The inclusion of these new species allowed us to refine both the evolutionary node of appearance of a number of microRNA genes/families, as well as MirGeneDBs phylogenetically informed nomenclature system. Updated covariance models of all microRNA families, along with all smallRNA read data are now downloadable. These enhanced annotations will allow researchers to analyze microRNA properties such as secondary structure and features of their biogenesis within a robust phylogenetic context and without the database plagued with numerous false positives and false negatives. In light of these improvements, MirGeneDB 3.0 will assume the responsibility for naming conserved novel metazoan microRNAs. MirGeneDB is part of RNAcentral and Elixir Norway, and is publicly and freely available at master.cloud.mirgenedb.org. Key PointsO_LIMajor update to the manually curated and uniformly named microRNA gene database MirGeneDB C_LIO_LI114 animal species, >1700 microRNA families and [~]20 000 genes searchable, browsable and downloadable C_LIO_LINew features to download all smallRNA read data and updated covariance models for each family C_LI

evolutionary biology↗

bioRxiv2024

Multi-View Integrative Approach For Imputing Short-Chain Fatty Acids and Identifying Key factors predicting Blood SCFA

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fiber within gastrointestinal tract. SCFAs produced by gut microbiotas (GMs) are absorbed by host, reach bloodstream, and are distributed to different organs, thus influencing host physiology. However, due to the limited budget or the poor sensitivity of instruments, most studies on GMs have incomplete blood SCFA data, limiting our understanding of the metabolic processes within the host. To address this gap, we developed an innovative multi-task multi-view integrative approach (M2AE, Multi-task Multi-View Attentive Encoders), to impute blood SCFA levels using gut metagenomic sequencing (MGS) data, while taking into account the intricate interplay among the gut microbiome, dietary features, and host characteristics, as well as the nuanced nature of SCFA dynamics within the body. Here, each view represents a distinct type of data input (i.e., gut microbiome compositions, dietary features, or host characteristics). Our method jointly explores both view-specific representations and cross-view correlations for effective predictions of SCFAs. We applied M2AE to two in-house datasets, which both include MGS and blood SCFAs profiles, host characteristics, and dietary features from 964 subjects and 171 subjects, respectively. Results from both of two datasets demonstrated that M2AE outperforms traditional regression-based and neural-network based approaches in imputing blood SCFAs. Furthermore, a series of gut bacterial species (e.g., Bacteroides thetaiotaomicron and Clostridium asparagiforme), host characteristics (e.g., race, gender), as well as dietary features (e.g., intake of fruits, pickles) were shown to contribute greatly to imputation of blood SCFAs. These findings demonstrated that GMs, dietary features and host characteristics might contribute to the complex biological processes involved in blood SCFA productions. These might pave the way for a deeper and more nuanced comprehension of how these factors impact human health.

bioinformatics↗