Biology subjects

Sun, Q.

Publications and source records attributed to Sun, Q..

At least 91 records · Page 5Linked to original sources

bioRxiv2024

Differential Proteomic Analysis of AML Patients at Low and Intermediate Altitudes after Chemotherapy

Chemotherapy is the primary treatment for patients with acute myeloid leukemia (AML). In addition to factors such as patient age, physical condition, and choice of medication, we have noticed that environmental factors such as altitude may also have a significant impact on post-chemotherapy bone marrow suppression in AML patients in clinical practice. The results indicate that there are differences in the proteomics of the two groups of patients during the bone marrow suppression period after chemotherapy. Differentially expressed proteins are primarily located in the cytoplasm, extracellular space, and nucleus, followed by mitochondria and membranes. These differentially expressed proteins mainly participate in biological processes such as cell and metabolism. For differential protein KEGG pathway enrichment analysis, it was found that metabolic pathways were mainly enriched in the metabolic category, while the PI3K-Akt signaling pathway, HIF-1 signaling pathway, NF-{kappa}B signaling pathway, and calcium signaling pathway were enriched in the signaling pathways.

cancer biology↗

bioRxiv2024

Comparative genomics of macaques and integrated insights into genetic variation and population history

The crab-eating macaques (Macaca fascicularis) and rhesus macaques (M. mulatta) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is [~]42% lower, while centromeres are [~]3.7 times longer than those in humans. The characterization of [~]2 Mbp fixed genetic variants and [~]240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g., CYP2C76 and EHBP1L1). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g., PNPO). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g., FOLH1 and PIEZO2). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g., STAB1, SEMA3F, and HOXD13). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.

genomics↗

bioRxiv2024

Cross-species alignment along the chronological axis reveals evolutionary effect on structural development of human brain

Disentangling evolution mysteries of human brain has always been an imperative endeavor in neuroscience. On the one hand, by spatially aligning the brains between human and nonhuman primates (NHPs), previous efforts in comparative studies revealed both correspondence and difference in brain anatomy, e.g., the morphological and the connectomic patterns. On the other hand, brain anatomical development along the temporal axis is evident for both human and NHPs in early life. However, it remains largely unknown whether we can conjugate the brain development phases between human and NHPs, and, especially, what the role played by the brain anatomy in the conjugation will be. Here, we proposed to embed the brain anatomy of human and macaque in the chronological axis for enabling the cross-species comparison on brain development. Specifically, we separately established the prediction models by using the brain anatomical features in gray matter and white matter tracts to predict the chronological age in the human and macaque samples with brain development. We observed that applying the trained models within-species could well predict the chronological age. Interestingly, by conducting the cross-species application of the trained models, e.g., applying the model trained in humans to the data of macaques, we found a significant cross-species imbalance regarding to the model performance, in which the model trained in macaque showed a higher accuracy in predicting the chronological age of human than the model trained in human in predicting the chronological age of macaque. The cross application of the trained model introduced the brain cross-species age gap (BCAP) as an individual index to quantify the cross-species discrepancy along the temporal axis of brain development for each participant. We further showed that BCAP was associated with the behavioral performance in both visual sensitivity test and picture vocabulary test in the human samples. Taken together, our study situated the cross-species brain development along the chronological axis, which highlighted the disproportionately anatomical development in the human brain to extend our understanding of the potential evolutionary effects.

neuroscience↗

bioRxiv2024

CD81+ fibroblasts, a unique subpopulation with accelerated cellular senescence, exaggerate inflammation and activate neutrophils via C3/C3aR1 axis in periodontitis

Periodontitis, a prevalent inflammatory disease worldwide, poses a significant economic burden on society and the country. Previous research has established a connection between cellular senescence and periodontitis. However, the role and mechanism of cell senescence in the progression of periodontitis have not been thoroughly investigated. This study aimed to explore the involvement of cellular senescence in the pathogenesis of periodontitis and determine the underlying mechanisms. Our findings demonstrated that senescent cells accumulated during the progress of periodontitis. Moreover, several scRNA-seq analysis suggested that gingival fibroblasts were the main cell population undergoing cellular senescence during periodontitis, which helps mitigate tissue damage and bone loss. Furthermore, we identified a high expression of CD81 in the senescent gingival fibroblast population. These cells were found to actively contribute to inflammation through their potent pro-inflammatory metabolic activity and secretion of SASP-related factors. Additionally, they recruited neutrophils via the C3/C3aR1 pathway, indirectly sustaining the inflammatory response. Senolytics via Navitoclax successfully alleviated inflammation and bone loss in periodontitis and administration of metformin could alleviate alleviated inflammation and bone loss in periodontitis through inhibiting cellular senescence. These results provide valuable insights into the cellular and molecular basis of periodontitis-induced tissue damage, highlighting the significance of fibroblast senescence. In conclusion, our study sheds light on the relationship between CD81 and cellular senescence, suggesting its potential as a therapeutic target for periodontitis.

immunology↗

bioRxiv2024

Genetic polymorphisms of Leukocyte Immunoglobulin-Like Receptor B3 (LILRB3) gene in African American kidney transplant recipients are associated with post-transplant graft failure

BackgroundAfrican American (AA) kidney transplant recipients exhibit a higher rate of graft loss compared to other racial and ethnic populations, highlighting the need to identify causative factors underlying this disparity. MethodWe analyzed RNA sequences of pretransplant whole blood from subjects followed in three kidney transplant cohorts to identify single nucleotide polymorphisms (SNPs) associated with death censored graft loss (DCGL). We employed a meta-analysis to uncover key transcriptional signatures and pathways associated with the identified SNPs and used single cell RNA to define cellular specificity. We characterized SNP functions using in vitro immunological and survival assays and tested for associations between the identified SNPs and other immune-related diseases using a [~]30,100 subject, electronic health record (EHR)-linked database. ResultsWe uncovered a cluster of four consecutive missense SNPs in the Leukocyte Immunoglobulin-Like Receptor B3 (LILRB3, a negative immune response regulator) gene that strongly associated with DCGL. This LILRB3-4SNPs cluster encodes missense mutations at amino acids 617-618 proximal to a SHP-1/2 phosphatase-binding ITIM motif. LILRB3-4SNPs is specifically enriched within subjects of AA ancestry (8.6% prevalence vs 2.3% in Hispanic and 0.1% in European populations), is not linked to APOL1 G1/G2 alleles, and exhibited a strong association with DCGL. Analysis of PBMC and transplant biopsies from recipients with LILRB3-4SNPs showed evidence of enhanced adaptive immune responsiveness and ferroptosis-associated death in monocytes. Overexpression of the variant allele in THP-1 cells (macrophage line) induced augmented inflammation and ferroptosis, which were attenuated by a ferroptosis inhibitor, verifying a causal link. The LILRB3-4SNPs also associated with multiple systemic and organ-specific immune-related diseases in AAs, consistent with conferring a broadly relevant immune function. Conclusionthe LILRB3-4SNPs represent a functionally important, distinct genetic risk factor for kidney transplant outcome and development/severity of other immune-related diseases in patients of AA ancestry. Pharmacological targeting of ferroptosis should be tested to prevent or treat these disease processes in AA recipients carrying LILRB3-4SNPs.

genetics↗

bioRxiv2024

Skeletal Muscle Stem Cells Modulate Niche Function in Duchenne Muscular Dystrophy through YY1-CCL5 Axis

Stem cell activity is known to be tightly regulated by both intrinsic and extrinsic pathways but less is known about whether and how stem cells modulate their niche microenvironment. Adult skeletal muscle stem cells (MuSCs) are indispensable for muscle regeneration and also tightly regulated by macrophages (MPs) and fibro-adipogenic progenitors (FAPs) in the niche. Deregulated MuSC/MP/FAP interactions and the ensuing inflammation and fibrosis are hallmarks of dystrophic muscle. Here in this study we demonstrate that intrinsic deletion of transcription factor YY1 in MuSCs exacerbates dystrophic pathologies by altering the cellular composition and heterogeneity of MPs and FAPs. Further analysis reveals that the YY1 loss induces the expression of immune genes in MuSCs, including Ccl5. Augmented secretion of CCL5 from MuSCs promotes the recruitment of MPs via CCL5/CCR5 mediated crosstalk, which subsequently hinders the apoptosis and clearance of FAPs through elevated TGF{beta}1 accumulation. Maraviroc mediated pharmacological blockade of the CCL5/CCR5 axis effectively mitigates muscle dystrophy and improves muscle performance. Lastly, we further demonstrate that YY1 represses Ccl5 transcription in MuSCs by directly binding to its enhancer thus facilitating promoter-enhancer looping. Altogether, our study has demonstrated the previously unappreciated role of MuSCs in actively shaping their niche microenvironment through secreting immunomodulatory cytokines, and has also provided novel insight into the therapeutic intervention of muscle dystrophy.

cell biology↗

bioRxiv2023

The Zea mays PeptideAtlas; a new maize community resource

We developed the Maize PeptideAtlas resource (www.peptideatlas.org/builds/maize) to help solve questions about the maize proteome. Publicly available raw tandem mass spectrometry (MS/MS) data for maize were collected from ProteomeXchange and reanalyzed through a uniform processing and metadata annotation pipeline. These data are from a wide range of genetic backgrounds, including the inbred lines B73 and W22, many hybrids and their respective parents. Samples were collected from field trials, controlled environmental conditions, a range of (a)biotic conditions and different tissues, cell types and subcellular fractions. The protein search space included different maize genome annotations for the B73 inbred line from MaizeGDB, UniProtKB, NCBI RefSeq and for the W22 inbred line. 445 million MS/MS spectra were searched, of which 120 million were matched to 0.37 million distinct peptides. Peptides were matched to 66.2% of the proteins (one isoform per protein coding gene) in the most recent B73 nuclear genome annotation (v5). Furthermore, most conserved plastid- and mitochondrial-encoded proteins (NCBI RefSeq annotations) were identified. Peptides and proteins identified in the other searched B73 genome annotations will aid to improve maize genome annotation. We also illustrate high confidence detection of unique W22 proteins. N-terminal acetylation, phosphorylation, ubiquitination, and three lysine acylations (K-acetyl, K-malonyl, K-hydroxyisobutyryl) were identified and can be inspected through a PTM viewer in PeptideAtlas. All matched MS/MS-derived peptide data are linked to spectral, technical and biological metadata. This new PeptideAtlas is integrated with community resources including MaizeGDB at https://www.maizegdb.org/ and a peptide track in JBrowse. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/572651v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1ec9005org.highwire.dtl.DTLVardef@1e35f34org.highwire.dtl.DTLVardef@7f5b2corg.highwire.dtl.DTLVardef@13acefd_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2023

Cellular distribution and motion of essential magnetosome proteins expressed in mammalian cells

Magnetosomes are organelle-like structures within magnetotactic bacteria that store iron biominerals in membrane-bound vesicles. In the bacteria, formation of these structures is highly regulated by approximately 30 genes which are conserved throughout different species. To compartmentalize iron in mammalian cells for magnetic resonance imaging using gene-based contrast, we are introducing key magnetosome proteins. We have previously expressed essential magnetosome genes mamI and mamL as fluorescent fusion proteins in the human melanoma cell line MDA-MB-435 and confirmed their co-localization and interaction. Here we investigate the expression of magnetosome genes mamB and mamE in MDA-MB-435 cells, using confocal fluorescence microscopy to observe expression patterns and to analyze particle mobility. Custom software was developed to characterize fluorescent particle trajectories. In mammalian cells, essential magnetosome proteins displayed different diffusive behaviours. However, all magnetosome proteins travelled at similar velocities when undergoing directed motion, suggesting that MamL, MamL+MamI, MamB, and MamE interact with similar mammalian mobile elements. These results confirm that localization and interaction of essential magnetosome proteins is tenable in the mammalian intracellular compartment.

synthetic biology↗

bioRxiv2023

Mutation of OsCDS5 confers broad-spectrum disease resistance in rice

Phospholipids are important components of biological membranes, participating in various biological processes, including plant development and responses to biotic and abiotic stresses. A previous study showed that mutation of the rice OsCDS5 (CDP-DAG Synthase) gene alters lipid metabolism, causing enhanced abiotic stress responses, yellowing of leaves at the seedling stage and delayed plant development. Here, we observed that the Oscds5 mutant shows enhanced resistance to rice blast, bacterial blight and bacterial leaf streak. Mutation of OsCDS5 promotes production of reactive oxygen species (ROS) and increases the expression level of multiple defense-related genes. Transcriptomic analyses indicate that genes involved in responses to stress, biotic/abiotic stimuli and metabolic processes are highly upregulated and enriched in mutant Oscds5. Metabolomic analyses show that differential metabolites are enriched in the lipid metabolic and tryptophan metabolic pathways. The decreased level of phosphatidylinositol (PI) and increased level of serotonin likely contribute to enhanced disease resistance of the Oscds5 mutant. Taken together, mutation of OsCDS5 enhances abiotic and biotic stress responses, and OsCDS5 may be a promising target in genetic engineering to enhance the resilience of rice to abiotic and biotic stresses simultaneously.

plant biology↗

bioRxiv2023

Essential magnetosome proteins MamI and MamL from magnetotactic bacteria interact in mammalian cells

To detect cellular activities deep within the body using magnetic resonance platforms, magnetosomes are the ideal model of genetically-encoded nanoparticles. These membrane-bound iron biominerals produced by magnetotactic bacteria are highly regulated by approximately 30 genes; however, only a few magnetosome genes are essential and may constitute the root structure upon which biominerals form. To test this, essential magnetosome genes mamI and mamL were expressed as fluorescent fusion proteins in mammalian cells. Localization and potential protein-protein interaction(s) were investigated using confocal microscopy and fluorescence correlation spectroscopy (FCS). Enhanced green fluorescent protein (EGFP)-MamI and the red fluorescent Tomato-MamL displayed distinct intracellular localization, with net-like and punctate fluorescence, respectively. Remarkably, co-expression revealed co-localization of both fluorescent fusion proteins in the same punctate pattern. An interaction between MamI and MamL was confirmed by co-immunoprecipitation. In addition, changes in EGFP-MamI distribution were accompanied by acquisition of intracellular mobility which all Tomato-MamL structures displayed. Truncation of the MamL C-terminal cationic peptide partially disrupted MamI-MamL colocalization but not mobility. Analysis of extracts from these cells by FCS was consistent with an interaction between fluorescent fusion proteins, including an increase in particle radius. Co-localization and interaction of MamI and MamL demonstrate that these essential magnetosome proteins may have a role in assembly of the magnetosome in any cell type.

synthetic biology↗

bioRxiv2023

Aberrant methylation and expression of TNXB promotes chondrocyte apoptosis and extracullar matrix degradation in hemophilic arthropathy via AKT signaling

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N = 5) and osteoarthritis (N = 5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

molecular biology↗

bioRxiv2023

Strong cascading impacts of micropollutants on planktonic food web in urban river

Urban rivers rely on intricate multitrophic interactions in food webs, which are vital for ecological functions. Human-induced pollutant discharge, notably micropollutants, poses a threat to these interactions. To study the impact of micropollutants on the microbial food web, we sampled downstream areas of the Jiulong Rivers north tributary (lower urbanization, [~]25% built land) and west tributary (higher urbanization, [~]65% built land) for eleven consecutive days in both dry and wet seasons in Fujian, China. We constructed a conceptualized planktonic food web model by employing DNA metabarcoding targeting bacteria, micro-eukaryotes (algae and protozoa), and microzooplankton. Our results revealed that the more urbanized west tributary exhibited significantly higher micropollutant concentrations. Structural equation modeling (SEM) incorporating micropollutants and all food web elements indicated a significantly stronger impact of micropollutants on the planktonic food web in the west tributary than in the north tributary. Micropollutants exhibited both direct and indirect (cascade) effects on high trophic levels (protozoa and microzooplankton), with algal communities mediating the cascade effects instead of bacterial communities, likely due to the increased eutrophication in the urbanized tributary. Overall, our study underscores the potential ecological disruptions caused by micropollutants in shaping planktonic food web interactions in urban rivers. SynopsisUrban rivers face ecological threats from micropollutants. This study shows elevated micropollutants significantly affected the planktonic food webs. Algal, rather than bacterial, food web pathway mediated micropollutants cascading effects on high trophic levels, emphasizing micropollutant-induced disruptions in urban rivers.

ecology↗

bioRxiv2023

Elucidating the molecular determinants for binding modes of a third-generation HIV-1 integrase strand transfer inhibitor: Importance of side chain and solvent reorganization

The first and second-generation clinically used HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) are key components of antiretroviral therapy (ART), which work by blocking the integration step in the HIV-1 replication cycle that is catalyzed by a nucleoprotein assembly called an intasome. However, resistance to even the latest clinically used INSTIs is beginning to emerge. Developmental third-generation INSTIs, based on naphthyridine scaffold, are promising candidates to combat drug-resistant viral variants. Among these novel INSTIs, compound 4f exhibits two distinct conformations when binding to intasomes from HIV-1 and the closely related prototype foamy virus (PFV), despite the high structural similarity of their INSTI binding pockets. The molecular mechanism and the key active site residues responsible for these differing binding modes in closely related intasomes remain elusive. To unravel the molecular determinants governing the two distinct binding modes, we employ a novel molecular dynamics-based free energy approach that utilizes alchemical pathways to overcome the sampling challenges associated with transitioning between two ligand conformations within crowded environments along physical pathways. The calculated conformational free energies successfully recapitulate the experimentally observed binding mode preferences in the two viral intasomes. Analysis of the simulated structures suggests that the observed binding mode preferences are caused by amino acid residue differences in both the front and the central catalytic sub-pocket of the INSTI binding site in HIV-1 and PFV. Additional free energy calculations on mutants of HIV-1 and PFV revealed that while both sub-pockets contribute to the binding mode selection, the central sub-pocket plays a more important role. These results highlight the importance of both side chain and solvent reorganization, as well as the conformational entropy in determining the ligand binding mode and will help inform the development of more effective INSTIs for combatting drug-resistant viral variants.

biophysics↗

bioRxiv2023

Dynamic floral scent profile of Epiphyllum oxypetalum and the cytosolic biosynthesis of trans-Geraniol through mevalonate pathway

O_LIEpiphyllum oxypetalum, a renowned ornamental species in Cactaceae, releases attractive fragrance during its infrequent, transient and nocturnal flowering, the nature and biosynthesis of the volatiles for this floral scent, however, remained unexplored. C_LIO_LIEmploying volatilomic, transcriptomic and biochemical approaches, we systematically characterized the composition, emission dynamics and biosynthesis of E. oxypetalum floral scent. C_LIO_LIFloral scent composition was highly dynamic, with trans-geraniol comprising 72.54% of the total emission at full bloom, followed by benzyl alcohol (12.96%) and methyl salicylate (3.75%), which predominantly emanated from petals and sepals. Transcriptomic analysis and inhibition assay using pathway-specific inhibitors revealed the mevalonate (MVA) pathway as the precursor source for trans-geraniol biosynthesis. Together with elevated expression of both cytosol-localized geraniol pyrophosphate synthase EoGDPS and geraniol synthase EoTPSa1, we elucidated an unusual cytosolic biosynthesis route for geraniol in E. oxypetalum petals. C_LIO_LIOur study on E. oxypetalum scent emission and its biosynthesis offers a comprehensive profile of cactus floral scent profiles and presents a rare case of cytosolic geraniol biosynthesis using MVA pathway-derived substrates. These findings underline the unique metabolism of cactus flower volatiles, which hold a promise to be applied in the development of novel perfumes. C_LI

plant biology↗

bioRxiv2023

Pervasive RNA Binding Protein Enrichment on TAD Boundaries Regulates TAD Organization

Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist to orchestrate TAD formation and maintenance. In this study, we investigate the potential role of RNA binding proteins (RBPs) in TAD organization. By integrated analyses of global RBP binding and 3D genome mapping profiles from both K562 and HepG2 cells, our study unveils the prevalent enrichment of RBPs on TAD boundaries and define boundary associated RBPs (baRBPs). We also characterize chromatin features of baRBP binding and uncover clustering among baRBPs and with transcription factors (TFs). Moreover, we found that baRBP binding is correlated with enhanced TAD insulation strength and in a CTCF independent manner. Further analyses revealed that baRBP binding is associated with nascent promoter transcription thus RBP/transcription may synergistically demarcate TADs. Additional experimental testing was performed using RBFox2 as a paradigm. Knockdown of RBFox2 in K562 cells causes remarkable TAD reorganization and boundary loss. Moreover, we found RBFox2 enrichment on TAD boundaries is a conserved phenomenon in C2C12 myoblast (MB) cells. RBFox2 is down-regulated and its bound boundaries are remodeled during MB differentiation into myotubes (MTs). Knockout of Rbfox2 in MBs also causes significant boundary reorganization. Finally, transcriptional inhibition in C2C12 cells indeed decreases RBFox2 binding and disrupts TAD boundary insulation. Altogether, our findings demonstrate that RBPs can play active role in modulating TAD organization through co-transcriptional association and synergistic action with nascent promoter transcripts.

bioinformatics↗

bioRxiv2023

Beyond the Colony-Forming-Unit: Rapid Bacterial Evaluation in Osteomyelitis

Examination of bacteria/host cell interactions is important for understanding the aetiology of many infectious diseases. The colony-forming-unit (CFU) has been the standard for quantifying bacterial burden for the past century, however, this suffers from low sensitivity and is dependent on bacterial culturability in vitro. Our data demonstrate the discrepancy between the CFU and bacterial genome copy number in an osteomyelitis-relevant co-culture system and we confirm diagnosis and quantify bacterial load in clinical bone specimens. This study provides an improved workflow for the quantification of bacterial burden in such cases.

microbiology↗

bioRxiv2023

Microbiome-based correction of nutrient profiles derived from self-reported dietary assessments

Since dietary intake is challenging to directly measure in large-scale cohort studies, we often rely on self-reported instruments (e.g., food frequency questionnaires, 24-hour recalls, and diet records) developed in nutritional epidemiology. Those self-reported instruments are prone to measurement errors, which can lead to inaccuracies in the calculation of nutrient profiles. Currently, few computational methods exist to address this problem. In the present study, we introduce a deep-learning approach --- Microbiome-based nutrient profile corrector (METRIC), which leverages gut microbial compositions to correct random errors in self-reported dietary assessments using 24-hour recalls or diet records. We demonstrate the excellent performance of METRIC in minimizing the simulated random errors, particularly for nutrients metabolized by gut bacteria in both synthetic and three real-world datasets. Further research is warranted to examine the utility of METRIC to correct actual measurement errors in self-reported dietary assessment instruments.

microbiology↗

bioRxiv2023

Paternal genomic resources from the YanHuang cohort suggested a Weakly-Differentiated Multi-source Admixture model for the formation of Hans founding ancestral lineages

The large-scale human genome revolution and rapidly advanced statistical innovation have updated our understanding of the fine-scale and complex genetic structure, the entire landscape of genetic diversity and the evolutionary trajectories of spatiotemporally different ancients and ethnolinguistically diverse modern populations. Recent ancient DNA research provided a detailed and complex admixture picture of ancient Europeans but limited insights into East Asians as the few available genomes. Y-chromosome variations in the male-specific regions, served as molecular archaeological tool, have unique evolutionary features that can be utilized to reconstruct the origin and subsequent interaction of ancient East Asian paternal lineages. We launched the YanHuang cohort using our designed highest-resolution capture sequencing panel to explore the detailed evolutionary trajectory of the Han Chinese, one of the largest ethnic groups in the world. We reported one of the largest uniparental genomic resources and observed multiple founding paternal lineages dominant in ancient western Eurasian, Siberian and East Asian participating in the formation of the gene pool of the Han Chinese. We identified fine-scale paternal genetic structure correlated with different patterns of ancient population interaction and geographical mountain barriers (Qinling-Huaihe line and Nanling Mountains), suggesting isolation-enhanced and admixture-introduced genetic differentiation enhanced the complexity of the Han Chinese genomic diversity. We observed a strong direct correlation between the frequency of multiple founding lineages of the Han Chinese and the proportion of subsistence-related ancestry sources related to western pastoralists, Holocene Mongolian Plateau people and ancient East Asians, reflecting the ancient migration events contributed to our identified patterns of Chinese paternal genomic diversity. We finally provided one novel and the most plausible admixture-by-admixture model, the Weakly-Differentiated Multi-Source Admixture model, as the major genetic mechanism to illuminate our observed pattern of complex interactions of multiple ancestral sources and landscape of the Han Chinese paternal genetic diversity. Generally, we presented one large-scale uniparental genomic resource from the YanHuang cohort, portrayed one novel admixture formation model and presented the entire genomic landscape with multiple ancestral sources related to ancient herders, hunter-gatherers and farmers who participated in the ancestral formation of the Han Chinese.

evolutionary biology↗