Near-Duplicate Image Retrieval Based on Contextual Descriptor

The state of the art of technology for near-duplicate image retrieval is mostly based on the Bag-of-Visual-Words model. However, visual words are easy to result in mismatches because of quantization errors of the local features the words represent. In order to improve the precision of visual words matching, contextual descriptors are designed to strengthen their discriminative power and measure the contextual similarity of visual words. This paper presents a new contextual descriptor that measures the contextual similarity of visual words to immediately discard the mismatches and reduce the count of candidate images. The new contextual descriptor encodes the relationships of dominant orientation and spatial position between the referential visual words and their context. Experimental results on benchmark Copydays dataset demonstrate its efficiency and effectiveness for near-duplicate image retrieval

Profiling a Community-Specific Function Landscape for Bacterial Peptides Through Protein-Level Meta-Assembly and Machine Learning

Small proteins, encoded by small open reading frames, are only beginning to emerge with the current advancement of omics technology and bioinformatics. There is increasing evidence that small proteins play roles in diverse critical biological functions, such as adjusting cellular metabolism, regulating other protein activities, controlling cell cycles, and affecting disease physiology. In prokaryotes such as bacteria, the small proteins are largely unexplored for their sequence space and functional groups. For most bacterial species from a natural community, the sample cannot be easily isolated or cultured, and the bacterial peptides must be better characterized in a metagenomic manner. The bacterial peptides identified from metagenomic samples can not only enrich the pool of small proteins but can also reveal the community-specific microbe ecology information from a small protein perspective. In this study, metaBP (Bacterial Peptides for metagenomic sample) has been developed as a comprehensive toolkit to explore the small protein universe from metagenomic samples. It takes raw sequencing reads as input, performs protein-level meta-assembly, and computes bacterial peptide homolog groups with sample-specific mutations. The metaBP also integrates general protein annotation tools as well as our small protein-specific machine learning module metaBP-ML to construct a full landscape for bacterial peptides. The metaBP-ML shows advantages for discovering functions of bacterial peptides in a microbial community and increases the yields of annotations by up to five folds. The metaBP toolkit demonstrates its novelty in adopting the protein-level assembly to discover small proteins, integrating protein-clustering tool in a new and flexible environment of RBiotools, and presenting the first-time small protein landscape by metaBP-ML. Taken together, metaBP (and metaBP-ML) can profile functional bacterial peptides from metagenomic samples with potential diverse mutations, in order to depict a unique landscape of small proteins from a microbial community

Genome-Resolved Proteomic Stable Isotope Probing of Soil Microbial Communities Using 13CO2 and 13C-Methanol.

Stable isotope probing (SIP) enables tracking the nutrient flows from isotopically labeled substrates to specific microorganisms in microbial communities. In proteomic SIP, labeled proteins synthesized by the microbial consumers of labeled substrates are identified with a shotgun proteomics approach. Here, proteomic SIP was combined with targeted metagenomic binning to reconstruct metagenome-assembled genomes (MAGs) of the microorganisms producing labeled proteins. This approach was used to track carbon flows from 13CO2 to the rhizosphere communities of Zea mays, Triticum aestivum, and Arabidopsis thaliana. Rhizosphere microorganisms that assimilated plant-derived 13C were capable of metabolic and signaling interactions with their plant hosts, as shown by their MAGs containing genes for phytohormone modulation, quorum sensing, and transport and metabolism of nutrients typical of those found in root exudates. XoxF-type methanol dehydrogenases were among the most abundant proteins identified in the rhizosphere metaproteomes. 13C-methanol proteomic SIP was used to test the hypothesis that XoxF was used to metabolize and assimilate methanol in the rhizosphere. We detected 7 13C-labeled XoxF proteins and identified methylotrophic pathways in the MAGs of 8 13C-labeled microorganisms, which supported the hypothesis. These two studies demonstrated the capability of proteomic SIP for functional characterization of active microorganisms in complex microbial communities

Variations in CD14 Gene Are Associated With Autoimmune Thyroid Diseases in the Chinese Population

Autoimmune thyroid diseases (AITDs) are chronic organ-specific autoimmune diseases and mainly include Graves' disease (GD) and Hashimoto's thyroiditis (HT). CD14 is an important component of the immune system as a receptor for gram-negative lipopolysaccharide (LPS). The genetic polymorphisms of CD14 have been confirmed to be associated with a variety of autoimmune diseases. However, its relationship with AITDs is still unclear. The study was aimed to determine whether four single nucleotide polymorphisms (rs2915863, rs2569190, rs2569192, and rs2563298) of CD14 are associated with AITDs and its subgroups of GD and HT. The results showed significant association of rs2915863 and rs2569190 with GD. The frequencies of rs2915863 genotypes and T allele in patients with GD differed significantly from their controls (P = 0.007 and P = 0.021, respectively). For rs2569190, frequencies of genotypes and G allele in GD patients also showed positive P-values (P = 0.038 and P = 0.027, respectively). The correlations between these two loci and GD are more pronounced in female GD patients and patients with a family history. In genetic model analysis, the allele model, recessive model, and homozygous model of rs2569190 and rs2915863 embodied strong correlations with GD after the adjusting of age and gender (P = 0.014, P = 0.015, P = 0.009, and P = 0.014, P = 0.001, P = 0.006, respectively). However, these four sites are not related to HT. We firstly discovered the relationship between CD14 gene polymorphism and GD, and the results indicate that CD14 is an important risk locus for AITD and its SNPs may contribute to host's genetic predisposition to GD

A Combined Risk Score Model to Assess Prognostic Value in Patients with Soft Tissue Sarcomas

A study by Tsvetkov et al. recently published a proposed novel form of copper-induced cell death in Science; however, few studies have looked into the possible mechanism in soft tissue sarcoma (STS). Herein, this study sought to investigate the function of cuproptosis-related genes (CRGs) in the development of tumor-associated immune cells and the prognosis of sarcoma. Herein, this study aimed to explore the role of cuproptosis-related genes (CRGs) in the development, tumor-associated immune cells, and the prognosis of sarcoma. Methods: The prognostic model was established via the least absolute shrinkage and selection operator (LASSO) algorithm as well as multivariate Cox regression analysis. The stromal scores, immune scores, ESTIMA scores, and tumor purity of sarcoma patients were evaluated by the ESTIMATE algorithm. Functional analyses were performed to investigate the underlying mechanisms of immune cell infiltration and the prognosis of CRGs in sarcoma. Results: Two molecular subgroups with different CRG expression patterns were recognized, which showed that patients with a higher immune score and more active immune status were prone to have better prognostic survival. Moreover, GO and KEGG analyses showed that these differentially expressed CRGs were mainly enriched in metabolic/ions-related signaling pathways, indicating that CRGs may have impacts on the immune cell infiltration and prognosis of sarcoma via regulating the bioprocess of mitochondria and consequently affecting the immune microenvironment. The expression levels of CRGs were closely correlated to the immunity condition and prognostic survival of sarcoma patients. Conclusions: The interaction between cuproptosis and immunity in sarcoma may provide a novel insight into the study of molecular mechanisms and candidate biomarkers for the prognosis, resulting in effective treatments for sarcoma patients

Inhibition of Nonsense-Mediated mRNA Decay by Antisense Morpholino Oligonucleotides Restores Functional Expression of hERG Nonsense and Frameshift Mutations in Long-QT Syndrome

Mutations in the human ether-a-go-go-related gene (hERG) cause long-QT syndrome type 2 (LQT2). We previously described a homozygous LQT2 nonsense mutation Q1070X in which the mutant mRNA is degraded by nonsense-mediated mRNA decay (NMD) leading to a severe clinical phenotype. The degradation of the Q1070X transcript precludes the expression of truncated but functional mutant channels. In the present study, we tested the hypothesis that inhibition of NMD can restore functional expression of LQT2 mutations that are targeted by NMD. We showed that inhibition of NMD by RNA interference-mediated knockdown of UPF1 increased Q1070X mutant channel protein expression and hERG current amplitude. More importantly, we found that specific inhibition of downstream intron splicing by antisense morpholino oligonucleotides prevented NMD of the Q1070X mutant mRNA and restored the expression of functional Q1070X mutant channels. The restoration of functional expression by antisense morpholino oligonucleotides was also observed in LQT2 frameshift mutations. Our findings suggest that inhibition of NMD by antisense morpholino oligonucleotides may be a potential therapeutic approach for some LQT2 patients carrying nonsense and frameshift mutations

ZNF410 represses fetal globin by devoted control of CHD4/NuRD [preprint]

Major effectors of adult-stage fetal globin silencing include the transcription factors (TFs) BCL11A and ZBTB7A/LRF and the NuRD chromatin complex, although each has potential on-target liabilities for rational β-hemoglobinopathy therapeutic inhibition. Here through CRISPR screening we discover ZNF410 to be a novel fetal hemoglobin (HbF) repressing TF. ZNF410 does not bind directly to the γ-globin genes but rather its chromatin occupancy is solely concentrated at CHD4, encoding the NuRD nucleosome remodeler, itself required for HbF repression. CHD4 has two ZNF410-bound regulatory elements with 27 combined ZNF410 binding motifs constituting unparalleled genomic clusters. These elements completely account for ZNF410’s effects on γ-globin repression. Knockout of ZNF410 reduces CHD4 by 60%, enough to substantially de-repress HbF while avoiding the cellular toxicity of complete CHD4 loss. Mice with constitutive deficiency of the homolog Zfp410 are born at expected Mendelian ratios with unremarkable hematology. ZNF410 is dispensable for human hematopoietic engraftment potential and erythroid maturation unlike known HbF repressors. These studies identify a new rational target for HbF induction for the β-hemoglobin disorders with a wide therapeutic index. More broadly, ZNF410 represents a special class of gene regulator, a conserved transcription factor with singular devotion to regulation of a chromatin subcomplex

Sex Differences in the Associations of Obesity With Hypothyroidism and Thyroid Autoimmunity Among Chinese Adults

There is an intensive link between obesity and thyroid dysfunction, but this relationship in Asians is still unclear. This study was conducted to define the impact of obesity on risk of hypothyroidism and thyroid autoimmunity among Chinese adults. A population-based, cross-sectional study was carried out, which enrolled a total of 2,808 Chinese adults. To assess the associations of obesity with hypothyroidism and thyroid autoimmunity, odds ratio (ORs) with 95% confidence intervals (95%CIs) were calculated through logistic regression model, and the correlations of body mass index (BMI) with TPOAb and TGAb were also analyzed. Obese females had higher risk of hypothyroidism (22.7 vs. 15.0%; OR = 1.66, 95%CI 1.10–2.53; P = 0.02) and higher risk of subclinical hypothyroidism (22.1 vs. 13.4%; OR = 1.83, 95%CI 1.20–2.80; P = 0.005) than non-obese females. Multivariate logistic regression analysis found significant associations of obesity with hypothyroidism (Adjusted OR = 1.54, 95%CI 1.00–2.38; P = 0.05) and subclinical hypothyroidism (Adjusted OR = 1.69, 95%CI 1.09–2.63; P = 0.02) in females after adjustment for confounding factors. No association between obesity and hypothyroidism was observed in male participants. Spearman's correlation analysis suggested BMI was significantly and positively correlated with TPOAb (Spearman's r = 0.062, P = 0.022) in men but not in women. Linear regression analysis suggested an obviously positive correlation of BMI with TPOAb in men (β = 0.018, P = 0.015) and an obviously negative correlation of BMI with TGAb in women (β = −0.025, P = 0.012), respectively. The study suggests sex differences in the associations of obesity with hypothyroidism and thyroid autoimmunity among Chinese adults. Further studies are needed to better understand the exact mechanism of sex difference in the obesity-thyroid relationship

Aberrant Expressions of Co-stimulatory and Co-inhibitory Molecules in Autoimmune Diseases

Co-signaling molecules include co-stimulatory and co-inhibitory molecules and play important roles in modulating immune responses. The roles of co-signaling molecules in autoimmune diseases have not been clearly defined. We assessed the expressions of co-stimulatory and co-inhibitory molecules in autoimmune diseases through a bioinformatics-based study. By using datasets of whole-genome transcriptome, the expressions of 54 co-stimulatory or co-inhibitory genes in common autoimmune diseases were analyzed using Robust rank aggregation (RRA) method. Nineteen array datasets and 6 RNA-seq datasets were included in the RRA discovery study and RRA validation study, respectively. Significant genes were further validated in several autoimmune diseases including Graves' disease (GD). RRA discovery study suggested that CD160 was the most significant gene aberrantly expressed in autoimmune diseases (Adjusted P = 5.9E-12), followed by CD58 (Adjusted P = 5.7E-06) and CD244 (Adjusted P = 9.5E-05). RRA validation study also identified CD160 as the most significant gene aberrantly expressed in autoimmune diseases (Adjusted P = 5.9E-09). We further found that the aberrant expression of CD160 was statistically significant in multiple autoimmune diseases including GD (P < 0.05), and CD160 had a moderate role in diagnosing those autoimmune diseases. Flow cytometry confirmed that CD160 was differentially expressed on the surface of CD8+ T cells between GD patients and healthy controls (P = 0.002), which proved the aberrant expression of CD160 in GD at the protein level. This study suggests that CD160 is the most significant co-signaling gene aberrantly expressed in autoimmune diseases. Treatment strategy targeting CD160-related pathway may be promising for the therapy of autoimmune diseases

Community proteogenomics reveals the systemic impact of phosphorus availability on microbial functions in tropical soil.

Phosphorus is a scarce nutrient in many tropical ecosystems, yet how soil microbial communities cope with growth-limiting phosphorus deficiency at the gene and protein levels remains unknown. Here, we report a metagenomic and metaproteomic comparison of microbial communities in phosphorus-deficient and phosphorus-rich soils in a 17-year fertilization experiment in a tropical forest. The large-scale proteogenomics analyses provided extensive coverage of many microbial functions and taxa in the complex soil communities. A greater than fourfold increase in the gene abundance of 3-phytase was the strongest response of soil communities to phosphorus deficiency. Phytase catalyses the release of phosphate from phytate, the most recalcitrant phosphorus-containing compound in soil organic matter. Genes and proteins for the degradation of phosphorus-containing nucleic acids and phospholipids, as well as the decomposition of labile carbon and nitrogen, were also enhanced in the phosphorus-deficient soils. In contrast, microbial communities in the phosphorus-rich soils showed increased gene abundances for the degradation of recalcitrant aromatic compounds, transformation of nitrogenous compounds and assimilation of sulfur. Overall, these results demonstrate the adaptive allocation of genes and proteins in soil microbial communities in response to shifting nutrient constraints