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Zhang, S.

Publications and source records attributed to Zhang, S..

At least 505 records · Page 28Linked to original sources

Confidence-Enhanced Semi-supervised Learning for Mediastinal Neoplasm Segmentation

Automated segmentation of mediastinal neoplasms in preoperative computed tomography (CT) scans is critical for accurate diagnosis. Though convolutional neural networks (CNNs) have proven effective in medical imaging analysis, the segmentation of mediastinal neoplasms, which vary greatly in shape, size, and texture, presents a unique challenge due to the inherent local focus of convolution operations. To address this limitation, we propose a confidence-enhanced semi-supervised learning framework for mediastinal neoplasm segmentation. Specifically, we introduce a confidence-enhanced module that improves segmentation accuracy over indistinct tumor boundaries by assessing and excluding unreliable predictions simultaneously, which can greatly enhance the efficiency of exploiting unlabeled data. Additionally, we implement an iterative learning strategy designed to continuously refine the estimates of prediction reliability throughout the training process, ensuring more precise confidence assessments. Quantitative analysis on a real-world dataset demonstrates that our model significantly improves the performance by leveraging unlabeled data, surpassing existing semi-supervised segmentation benchmarks. Finally, to promote more efficient academic communication, the analysis code is publicly available at https://github.com/fxiaotong432/CEDS. Author summaryIn clinical practice, computed tomography (CT) scans can aid in the detection and evaluation of mediastinal tumors. The early detection of mediastinal tumors plays a crucial role in formulating appropriate treatment plans and improving patient survival rates. To reduce the high cost of manual annotation, researchers have attempted to employ convolutional neural networks (CNNs) for efficient automatic segmentation. However, the significant challenges arise due to the considerable variation in shape, size, and texture of mediastinal tumors, posing difficulties for the segmentation task. In this study, we introduce a confidence-enhanced module with a semi-supervised learning framework. By evaluating the models prediction confidence and selecting high-confidence predictions, we improve the efficiency and quality of data utilization. This approach demonstrates the achievement of accurate mediastinal tumor segmentation with only a minimal amount of labeled data. Our research not only provides an effective technical approach for automatic segmentation of mediastinal tumors but also opens up new possibilities for optimizing strategies in semi-supervised learning methods.

bioengineering↗

SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1

Although there is growing appreciation for effective repurposing of selective serotonin reuptake inhibitors (SSRIs) for cancer therapy, particularly hepatocellular carcinoma (HCC), efforts are hampered by limited knowledge of their molecular targets and mechanism of action. Global inverse gene-expression profiling method, drug affinity responsive target stability assay, and in silico molecular docking analysis was performed to identify the targets of SSRIs. Murine subcutaneous, orthotopic models, and patient-derived xenograft were employed to explore the therapeutic effects and underlying mechanisms of SSRIs in HCC. The clinical relevance of SSRI use was verified with real world data. SSRIs exhibit significant anti-HCC effects independent of their known target serotonin reuptake transporter. The glucose transporter 1 (GLUT1) is identified as a new target of SSRIs. Citalopram binds to and antagonizes GLUT1, resulting in reduced glycolytic flux and ATP generation. Mutant GLUT1 in the binding site E380 of citalopram compromises the inhibitory effects of citalopram on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth kinetics of GLUT1high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis of health records found that SSRIs use is associated with a lower risk of metastasis among HCC patients. Our study reveals an unprecedented role of SSRIs in cancer metabolism, and establishes a rationale for repurposing SSRIs as potential anticancer drugs for HCC.

cancer biology↗

Systematic Targeting of Protein Complexes with Molecular COUPLrs

Molecular glues that engage protein complexes have transformed the study of cell biology and have had a direct impact on clinical oncology. However, the identification of new glue classes and their corresponding protein complexes has remained largely serendipitous. To overcome this challenge, we report the development of molecular COUPLrs, elaborated small molecules flanked by two cysteine-reactive warheads, as well as CONNECT, an integrated chemical proteomic platform for target deconvolution. By profiling a library of molecular COUPLrs across 13 cancer cell lines, we uncovered hundreds of proteins that can be coupled together, including in some cases in mutant selective fashions. We develop an advanced COUPLr for the oncogene EML4-ALK, which engages the fusion outside of its kinase domain, restricts protein dynamics, and disrupts EML4-ALK signaling. Collectively, molecular COUPLrs substantially expand the scope of proteins that can be chemically connected, providing an unbiased approach to identify small molecules that target protein complexes.

systems biology↗

Stratifying variant deleteriousness and trait-modulating effect under human recent adaptation

Despite advances in annotating and interpreting human genetic variants, existing methods to distinguish deleterious/pathogenic from neutral variants still inadequately capture the nuanced impact of genetic variants on fitness and disease susceptibility. In this study, we introduced a new deep learning framework, the FIND model, by stratifying genetic variants into refined categories based on selection pressures and derived allele frequency. FIND demonstrated superior performance over existing genome-wide methods, delivering enhanced resolution in differentiating trait-modulating alleles from those that are pathogenic or neutral. Access to base-wise informative annotations has unveiled novel features that significantly enhance the model interpretability, and FIND has adeptly delineated evolutionary trends in human accelerated regions. Furthermore, applying FIND to the interpretation of clinical variants demonstrates its substantial potential in reclassifying variants of unknown significance. This work advances our understanding of the genetic underpinnings of human adaptation and disease, providing a new tool to explore the complexities of genetic contributions to health.

genetics↗

Msh3 and Pms1 Set Neuronal CAG-repeat Migration Rate to Drive Selective Striatal and Cortical Pathogenesis in HD Mice

Modifiers of Huntingtons disease (HD) include mismatch repair (MMR) genes; however, their underlying disease-altering mechanisms remain unresolved. Knockout (KO) alleles for 9 HD GWAS modifiers/MMR genes were crossed to the Q140 Huntingtin (mHtt) knock-in mice to probe such mechanisms. Four KO mice strongly (Msh3 and Pms1) or moderately (Msh2 and Mlh1) rescue a triad of adult-onset, striatal medium-spiny-neuron (MSN)-selective phenotypes: somatic Htt DNA CAG-repeat expansion, transcriptionopathy, and mHtt protein aggregation. Comparatively, Q140 cortex also exhibits an analogous, but later-onset, pathogenic triad that is Msh3-dependent. Remarkably, Q140/homozygous Msh3-KO lacks visible mHtt aggregates in the brain, even at advanced ages (20-months). Moreover, Msh3-deficiency prevents striatal synaptic marker loss, astrogliosis, and locomotor impairment in HD mice. Purified Q140 MSN nuclei exhibit highly linear age-dependent mHtt DNA repeat expansion (i.e. repeat migration), with modal-CAG increasing at +8.8 repeats/month (R2=0.98). This linear rate is reduced to 2.3 and 0.3 repeats/month in Q140 with Msh3 heterozygous and homozygous alleles, respectively. Our study defines somatic Htt CAG-repeat thresholds below which there are no detectable mHtt nuclear or neuropil aggregates. Mild transcriptionopathy can still occur in Q140 mice with stabilized Htt 140-CAG repeats, but the majority of transcriptomic changes are due to somatic repeat expansion. Our analysis reveals 479 genes with expression levels highly correlated with modal-CAG length in MSNs. Thus, our study mechanistically connects HD GWAS genes to selective neuronal vulnerability in HD, in which Msh3 and Pms1 set the linear rate of neuronal mHtt CAG-repeat migration to drive repeat-length dependent pathogenesis; and provides a preclinical platform for targeting these genes for HD suppression across brain regions. One Sentence SummaryMsh3 and Pms1 are genetic drivers of sequential striatal and cortical pathogenesis in Q140 mice by mediating selective CAG-repeat migration in HD vulnerable neurons.

neuroscience↗

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

Septins can function as scaffolds for protein recruitment, membrane-bound diffusion barriers, or membrane curvature sensors. Septins are important for cytokinesis, but their exact roles are still obscure. In fission yeast, four septins (Spn1 to Spn4) accumulate at the rim of the division plane as rings. The octameric exocyst complex, which tethers exocytic vesicles to the plasma membrane, exhibits a similar localization and is essential for plasma membrane deposition during cytokinesis. Without septins, the exocyst spreads across the division plane but absent from the rim during septum formation. These results suggest that septins and the exocyst physically interact for proper localization and function. Indeed, we predicted six pairs of interactions between septin and exocyst subunits by AlphaFold, most of them are confirmed by co-immunoprecipitation and yeast two-hybrid assays. Exocyst mislocalization results in mistargeting of secretory vesicles and their cargos, which leads to cell-separation delay in septin mutants. Our results indicate that septins guide the targeting of exocyst complex on the plasma membrane for vesicle tethering during cytokinesis through physical interactions.

cell biology↗

Dynamics and Regulatory Roles of RNA m6A Methylation in Unbalanced Genomes

N6-methyladenosine (m6A) in eukaryotic RNA is an epigenetic modification that is critical for RNA metabolism, gene expression regulation, and the development of organisms. Aberrant expression of m6A components appears in a variety of human diseases. RNA m6A modification in Drosophila has proven to be involved in sex determination regulated by Sxl and may affect X chromosome expression through the MSL complex. The dosage-related effects under the condition of genomic imbalance (i.e., aneuploidy) are related to various epigenetic regulatory mechanisms. Here, we investigated the roles of RNA m6A modification in unbalanced genomes using aneuploid Drosophila. The results showed that the expression of m6A components changed significantly under genomic imbalance, and affected the abundance and genome-wide distribution of m6A, which may be related to the developmental abnormalities of aneuploids. The relationships between methylation status and classical dosage effect, dosage compensation, and inverse dosage effect were also studied. In addition, we demonstrated that RNA m6A methylation may affect dosage-dependent gene regulation through dosage-sensitive modifiers, alternative splicing, the MSL complex, and other processes. More interestingly, there seems to be a closely relationship between MSL complex and RNA m6A modification. It is found that ectopically overexpressed MSL complex, especially the levels of H4K16Ac through MOF could influence the expression levels of m6A modification and genomic imbalance may be involved in this interaction. We found that m6A could affect the levels of H4K16Ac through MOF, a component of the MSL complex, and that genomic imbalance may be involved in this interaction. Altogether, our work reveals the dynamic and regulatory role of RNA m6A modification in unbalanced genomes, and may shed new light on the mechanisms of aneuploidy-related developmental abnormalities and diseases.

genomics↗

New Atg9 phosphorylation sites regulate autophagic trafficking in glia

We previously identified a role for dAuxilin (dAux), the fly homolog of Cyclin G-associated kinase (GAK), in glial autophagy contributing to Parkinsons disease (PD). To further dissect the mechanism, we present evidence here that lack of glial dAux enhanced the phosphorylation of the autophagy-related protein Atg9 at two newly identified threonine residues, T62 and T69. Enhanced Atg9 phosphorylation in the absence of glial dAux is potentially regulated through the master autophagy regulator Atg1, as the presence of which is required for Atg9 to interact with dAux in an otherwise separate condition. The enhanced Atg9 phosphorylation promotes autophagosome formation and Atg9 trafficking to the autophagosomes in glia. Whereas the expression of the non-phosphorylatable Atg9 variants suppresses the lack of dAux-induced increase in both autophagosome formation and Atg9 trafficking to autophagosome, the expression of the phophomimetic Atg9 variants restores the lack of Atg1-induced decrease in both events. Notably, Atg9 phosphorylation at T62 and T69 contributes to DA neurodegeneration and locomotor dysfunction implicated in PD. Thus, we have identified a dAux-Atg1-Atg9 axis relaying signals through the Atg9 phosphorylation at T62 and T69; these findings further elaborate the mechanism of dAux regulating glial autophagy and highlight the significance of protein degradation pathway in glia contributing to PD.

neuroscience↗

Rod-shaped microglia interact with neuronal dendrites to regulate cortical excitability in TDP-43 related neurodegeneration

Motor cortical hyperexcitability is well-documented in the presymptomatic stage of amyotrophic lateral sclerosis (ALS). However, the mechanisms underlying this early dysregulation are not fully understood. Microglia, as the principal immune cells of the central nervous system, have emerged as important players in sensing and regulating neuronal activity. Here we investigated the role of microglia in the motor cortical circuits in a mouse model of TDP-43 neurodegeneration (rNLS8). Utilizing multichannel probe recording and longitudinal in vivo calcium imaging in awake mice, we observed neuronal hyperactivity at the initial stage of disease progression. Spatial and single-cell RNA sequencing revealed that microglia are the primary responders to motor cortical hyperactivity. We further identified a unique subpopulation of microglia, rod-shaped microglia, which are characterized by a distinct morphology and transcriptional profile. Notably, rod-shaped microglia predominantly interact with neuronal dendrites and excitatory synaptic inputs to attenuate motor cortical hyperactivity. The elimination of rod-shaped microglia through TREM2 deficiency increased neuronal hyperactivity, exacerbated motor deficits, and further decreased survival rates of rNLS8 mice. Together, our results suggest that rod-shaped microglia play a neuroprotective role by attenuating cortical hyperexcitability in the mouse model of TDP-43 related neurodegeneration.

neuroscience↗

Early to Middle Pleistocene transition shapes the evolution of human-specific mutations associated with height and basal metabolic rate

Understanding the genetic basis of modern-human-specific traits is essential for elucidating the formation of anatomically modern humans (AMHs). Here, we studied the genetic underpinnings of height and basal metabolic rate (BMR), which have undergone extensive modifications in AMHs compared to other Homo species and apes. The results revealed a significant genetic correlation between the two traits. The evolution of the variants associated with height and BMR was heavily influenced by environmental factors, marked by two bursts during the Early to Middle Pleistocene transition and one afterward, accounting for 37.4% of the inferred causal variants for height and BMR. We identified an AMH-specific mutation, rs34590044-A, which emerged around 981,916 years ago, coinciding with the first burst of variants associated with increased height and BMR. rs34590044-A upregulates the expression of ACSF3 via increasing its enhancer activity, leading to increased mitochondrial function, body length, and BMR exclusively in mice fed essential amino acids, specifically threonine-enriched diets, which are characteristic of meat-based diets. Therefore, the emergence of rs34590044-A may contribute to the shift from an herbivorous to a carnivorous diet in AMHs. Our results underscore the complex interplay between genetics and environment in shaping the crucial phenotypes and physiological traits of AMHs.

genetics↗

Lipidic and senescent macrophages predict progression and response to combinatorial immunotherapy in triple-negative breast cancer

Immune cell subsets in the tumor predict prognosis. Identifying reliable subsets consistently in multiple patients is clinically important. Whats more advantageous to the field is if such subsets can be a target of immunotherapy. Here we analyzed single-cell RNA-sequencing datasets of patients with triple-negative breast cancer and identified APOE or FABP5-expressing macrophages correlated with poor prognosis. Further validation with TCGA-BRCA cohort detailed molecular signatures of these macrophages as lipidic and senescent. Our receptor-ligand mapping identified lipidic and senescent macrophages both suppress T-lymphoid and myeloid immunogenicity. Finally, we discovered that immune checkpoint therapy combined with chemotherapy reprogrammed anti-tumor microenvironment enriched with FOLR2+ macrophages facilitated T-cell activations. This suggests that lipidic and senescent macrophages could be a therapeutic target of immune checkpoint therapy.

cancer biology↗

A detailed analysis of 16S rRNA gene sequencing and conventional PCR-based testing for the diagnosis of bacterial pathogens and discovery of novel bacteria

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7% to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1% to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.

microbiology↗

A Multitrait Genome-Wide Association Study Reveals a Requirement for the Strigolactone Receptor DWARF14 in Optimal GOLVEN10 Signaling

GOLVEN/ROOT MERISTEM GROWTH FACTOR family of signaling peptides have been shown to control root lateral organ number, density and positioning in plants, although the signaling pathways involved remain obscure. A diverse set of 171 Medicago truncatula HapMap accessions with variation in responses to the GOLVEN 10 peptide, GLV10, were used to identify 74 significant loci controlling seven traits related to nodule formation and root architecture. Importantly, a single nucleotide polymorphism (SNP) in the upstream region of the MtGLV10 peptide-inducible strigolactone receptor gene, MtDWARF14 was significantly associated with insensitivity of nodule density to GLV10, suggesting a link between strigolactone signaling and GLV10 responsiveness. Three independent d14 mutants of the DWARF14 gene were found to hypernodulate, while overexpression of the gene led to reduction in nodule number, phenocopying GLV10. A null mutant, mtd14-1, remained sensitive to GLV10s effect on nodule density. However, at the transcriptional level, the mutant failed to effectively induce the expression of the GOLVEN marker genes, MtPLETHORA3 and MtPINLIKES2. Our study uncovers a hitherto unknown link between the strigolactone and GLV peptide signaling pathways using genotype x environment analysis of Medicago HapMap lines and provides a putative molecular mechanism for recovery from frost damage to fine roots.

plant biology↗

O-Glycosylated RNA Identification and Site-specific Prediction by Solid-phase Chemoenzymatic TnORNA method and PONglyRNA tool

Recent studies have shown that the cell surface undergoes post-transcriptional modification by N-linked glycosylation. However, the question of whether RNA can be glycosylated by O-glycans remains to be explored. The presence of O-glycosylation in cells is indirectly revealed by the presence of O-glycans on RNAs following treatment with O-glycoproteases. To identify RNA O-glycosylation, we have developed a chemoenzymatic method for capturing and enriching O-glycosylated RNA (O-glycoRNA) using covalent immobilization on a solid support. GalNAcEXO selectively releases Tn-containing O-glycosylated RNAs (TnORNA). Using this method and SPCgRNA, we compared the expression of O-glycoRNAs and N-glycoRNAs in pancreatic cancer cell lines and tissues. We found that glycosylated miR-103a-3p, miR-122-5p, and miR-4492 regulate pancreatic cancer cell growth and proliferation through the PI3K-Akt pathway. In vitro assays and PDAC tissue analysis confirmed the potential regulatory roles of Tn-O-glycosylated miRNAs in pancreatic tumor growth and metastasis. Furthermore, a significant number (131) of miRNAs carrying both N- and Tn-O-glycosylation were identified, indicating the co-occurrence of N-linked and O-linked glycosylation on small RNAs. We have also developed PONglyRNA, an online bioinformatic tool for the site-specific prediction of RNA glycosylation. PONglyRNA identifies glycosylation motifs based on RNA sequence and has been validated using our glycoRNA data. In conclusion, this study establishes robust experimental and computational tools for identifying O-linked glycoRNAs. Additionally, it uncovers the novel role of glycosylation in PDAC development and progression through altered glycosylation of oncogenic miRNAs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=195 HEIGHT=200 SRC="FIGDIR/small/599663v1_ufig1.gif" ALT="Figure 1"> View larger version (72K): org.highwire.dtl.DTLVardef@199511corg.highwire.dtl.DTLVardef@9c3338org.highwire.dtl.DTLVardef@e6d315org.highwire.dtl.DTLVardef@2c1fc1_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

Unveiling the mechanisms of black phosphorus nanosheets-induced viable but non-culturable state in Bacillus tropicus

The release of black phosphorus (BP) nanosheets has raised concerns regarding potential ecological risks. Previous studies have confirmed their toxicity to bacteria, but discrepancies were observed between results obtained from the growth curve and colony forming unit (CFU) methods, indicating the possibility of bacterial cells entering a viable but non-culturable (VBNC) state induced by BP nanosheets. To accurately assess the risks, it is crucial to understand the underlying mechanisms. In this study, we investigated the effect of BP nanosheets on Bacillus tropicus, a gram-positive bacterium, using transcriptome sequencing and biological assays. Our findings revealed that BP nanosheets caused minimal cell death but predominately induced the VBNC state in most cells. At the transcriptional level, we observed significant down-regulation of pathways associated with cellular metabolism and respiratory chain in response to BP nanosheet treatment. Bacterial cells in the VBNC state exhibited depressed respiration to maintain basal cellular activity. Additionally, the reduced cellular respiration and metabolic activity were associated with a decrease in antibiotic susceptibility of the bacteria. These results provide new insights into the antibacterial mechanisms of BP nanosheets and emphasize the necessity of employing appropriate approaches, beyond the traditional CFU method, to assess the bacterial toxicity of nanomaterials. Environmental implicationBacteria play a crucial role as indicators in ecological risk assessment. Although numerous studies have highlighted the exceptional antibacterial properties of black phosphorus (BP) nanosheets, the unique viable but non-culturable (VBNC) state of bacteria is often overlooked when evaluating the ecological risks of nanomaterial, including BP nanosheets. In our study, we found that BP nanosheets can induce Bacillus tropicus into a VBNC state by suppressing cellular metabolism- and respiratory chain-related pathways, shedding light on their ecological risk assessment implications. This finding underscores the importance of utilizing appropriate approaches in evaluating the bacterial toxicity of nanomaterials.

pharmacology and toxicology↗

Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer

Proteasome is an essential organelle in guarding cellular protein homeostasis. Here, we report that inhibition of proteasome leads to alterations in DNA methylation patterns in colorectal cancer (CRC) by surpressing the synthesis of DNA methyltransferases (DNMTs). We found that treating CRC cells with proteasome inhibitors results in attenuated translation of DNMT1 and DNMT3B, mediated by the inactivation of AKT and mammalian target of rapamycin (mTOR), which is dependent on the accumulation of p300, an acetyltransferase that inhibits AKT through acetylation modification. Furthermore, we demonstrated that downregulation of DNMT1 and DNMT3B confers protection against proteasome inhibitor treatment, potentially through reprogramming the transcriptome of CRC cells, highlighting the significant role of DNMTs in response to disruptions in protein homeostasis. Interestingly, the proteasome inhibitor-induced downregulation of DNMT1 and DNMT3B appears to be CRC specific, notwithstanding the underlying mechanism remains unclear. Altogether, our findings reveal an epigenetic effect of proteasome on DNA methylation in CRC through its regulation of DNA methyltransferase synthesis.

cancer biology↗

Durable Antimicrobial Microstructure Surface (DAMS) Enabled by 3D-Printing and ZnO Nanoflowers

A.Numerous studies have been trying to create nanomaterials based antimicrobial surfaces to combat the growing bacterial infection problems. Mechanical durability has become one of the major challenges to applying those surfaces in real life. In this study, we demonstrate the Durable Antimicrobial Microstructures Surface (DAMS) consisting of DLP 3D printed microstructures and zinc oxide (ZnO) nanoflowers. The microstructures serve as a protection armor for the nanoflowers during abrasion. The antimicrobial ability was tested by immersing in 2E8 CFU/mL Escherichia coli (E. coli) suspension and then evaluated using electron microscopy. Compared to the bare control, our results show that the DAMS reduces bacterial coverage by more than 90% after 12 hrs of incubation and approximately 50% after 48 hrs of incubation before abrasion. Importantly, bacterial coverage is reduced by approximately 50% after 2 min of abrasion with a tribometer, and DAMS remains effective even after 6 min of abrasion. These findings highlight the potential of DAMS as an affordable, scalable, and durable antimicrobial surface for various biomedical applications.

bioengineering↗

Uncovering topologically associating domains from three-dimensional genome maps with TADGATE

Topologically associating domains (TADs) emerge as indispensable units in three-dimensional (3D) genome organization, playing a critical role in gene regulation. However, accurately identifying TADs from sparse chromatin contact maps and exploring the structural and functional elements within TADs remain challenging. To this end, we develop a graph attention auto-encoder, TADGATE, to accurately identify TADs even from ultra-sparse contact maps and generate the imputed maps while preserving or enhancing the underlying topological structures. TADGATE can capture specific attention patterns, pointing to two types of units with different characteristics in TADs. Moreover, we find that the organization of TADs is closely associated with chromatin compartmentalization, and TAD boundaries in different compartmental environments exhibit distinct biological properties. We also utilize a two-layer Hidden Markov Model to functionally annotate the TADs and their internal regions, revealing the overall properties of TADs and the distribution of the structural and functional elements within TADs. At last, we apply TADGATE to highly sparse and noisy Hi-C contact maps from 21 human tissues or cell lines, enhancing the clarity of TAD structures, investigating the nature of conserved and cell type-specific boundaries, and unveiling the cell type-specific transcriptional regulatory mechanisms associated with topological domains.

bioinformatics↗