Identification of cancer driver genes based on hierarchical weak consensus model.

Cancer is a complex gene mutation disease that derives from the accumulation of mutations during somatic cell evolution. With the advent of high-throughput technology, a large amount of omics data has been generated, and how to find cancer-related driver genes from a large number of omics data is a challenge. In the early stage, the researchers developed many frequency-based driver genes identification methods, but they could not identify driver genes with low mutation rates well. Afterwards, researchers developed network-based methods by fusing multi-omics data, but they rarely considered the connection among features. In this paper, after analyzing a large number of methods for integrating multi-omics data, a hierarchical weak consensus model for fusing multiple features is proposed according to the connection among features. By analyzing the connection between PPI network and co-mutation hypergraph network, this paper firstly proposes a new topological feature, called co-mutation clustering coefficient (CMCC). Then, a hierarchical weak consensus model is used to integrate CMCC, mRNA and miRNA differential expression scores, and a new driver genes identification method HWC is proposed. In this paper, the HWC method and current 7 state-of-the-art methods are compared on three types of cancers. The comparison results show that HWC has the best identification performance in statistical evaluation index, functional consistency and the partial area under ROC curve. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-024-00279-6.

Comparison of lipidome profiles in human milk from Chinese Han and Korean ethnic groups based on UPLC-QTRAP-MS/MS.

The composition of milk lipids varies across different ethnic sources. The lipidome profiles of Chinese Han human milk (HHM) and Chinese Korean human milk (KHM) were investigated in this study. A total of 741 lipids were identified in HHM and KHM. Twenty-eight differentially expressed lipids (DELs) were screened between the 2 milk groups; among these, 6 triacylglycerols (TGs), 13 diacylglycerols (DGs), 7 free fatty acids (FFAs), and 1 monoglyceride (MG) were upregulated in KHM. Carnitine (CAR) was upregulated in HHM. Most DELs showed a single peak distribution in both groups. The correlations, related pathways and diseases of these DELs were further analyzed. The results demonstrated that DG, MG, and FFAs showed highly positive correlations with each other (r >0.8). The most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) and Human Metabolome Database (HMDB) pathways were inositol phosphate metabolism, and α-linolenic acid and linolenic acid metabolism, respectively. Major depressive disorder-related FFA (20:5) and FFA (22:6) were more abundant in KHM, while HHM showed more obesity-related CAR. These data potentially provide lipidome information regarding human milk from different ethnicities in China.

Mdwgan-gp: data augmentation for gene expression data based on multiple discriminator WGAN-GP.

BACKGROUND: Although gene expression data play significant roles in biological and medical studies, their applications are hampered due to the difficulty and high expenses of gathering them through biological experiments. It is an urgent problem to generate high quality gene expression data with computational methods. WGAN-GP, a generative adversarial network-based method, has been successfully applied in augmenting gene expression data. However, mode collapse or over-fitting may take place for small training samples due to just one discriminator is adopted in the method. RESULTS: In this study, an improved data augmentation approach MDWGAN-GP, a generative adversarial network model with multiple discriminators, is proposed. In addition, a novel method is devised for enriching training samples based on linear graph convolutional network. Extensive experiments were implemented on real biological data. CONCLUSIONS: The experimental results have demonstrated that compared with other state-of-the-art methods, the MDWGAN-GP method can produce higher quality generated gene expression data in most cases.

Essential proteins discovery based on dominance relationship and neighborhood similarity centrality.

Essential proteins play a vital role in development and reproduction of cells. The identification of essential proteins helps to understand the basic survival of cells. Due to time-consuming, costly and inefficient with biological experimental methods for discovering essential proteins, computational methods have gained increasing attention. In the initial stage, essential proteins are mainly identified by the centralities based on protein-protein interaction (PPI) networks, which limit their identification rate due to many false positives in PPI networks. In this study, a purified PPI network is firstly introduced to reduce the impact of false positives in the PPI network. Secondly, by analyzing the similarity relationship between a protein and its neighbors in the PPI network, a new centrality called neighborhood similarity centrality (NSC) is proposed. Thirdly, based on the subcellular localization and orthologous data, the protein subcellular localization score and ortholog score are calculated, respectively. Fourthly, by analyzing a large number of methods based on multi-feature fusion, it is found that there is a special relationship among features, which is called dominance relationship, then, a novel model based on dominance relationship is proposed. Finally, NSC, subcellular localization score, and ortholog score are fused by the dominance relationship model, and a new method called NSO is proposed. In order to verify the performance of NSO, the seven representative methods (ION, NCCO, E_POC, SON, JDC, PeC, WDC) are compared on yeast datasets. The experimental results show that the NSO method has higher identification rate than other methods.

Curcumin-mediated photodynamic treatment extends the shelf life of salmon (Salmo salar) sashimi during chilled storage: Comparisons of preservation effects with five natural preservatives.

The impact of curcumin-mediated photodynamic treatment (PDT) on the microbiological, physicochemical and sensory qualities of salmon sashimi has not been explored. Herein, this study aimed to evaluate the effects of PDT on the shelf-life quality of ready-to-eat salmon fillets during chilled storage (4 °C) in comparison with five widely investigated natural extracts, including cinnamic aldehyde, rosmarinic acid, chlorogenic acid, dihydromyricetin and nisin. From a microbial perspective, PDT exhibited outstanding bacterial inhibition, the results of total viable counts, total coliform bacteria, psychrotrophic bacteria, Pseudomonas spp., Enterobacteriaceae family, and H2S-producing bacteria were notably inactivated (p < 0.05) to meet the acceptable limits by PDT in comparison with those of the control group and natural origin groups, which could extend the shelf-life of salmon fillets from<6 days to 10 days. In the alteration of physicochemical indicators, PDT and natural extracts were able to maintain the pH value and retard lipid oxidation in salmon fillets, while apparently slowing the accumulation (p < 0.05) of total volatile basic nitrogen and biogenic amines, especially the allergen histamine, which contrary to with the variation trend of spoilage microbiota. In parallel, PDT worked effectively (p < 0.05) on the breakdown of adenosine triphosphate and adenosine diphosphate to maintain salmon fillet freshness. Additionally, the physical indicators of texture profile and color did not have obvious changes (p < 0.05) after treated by PDT during the shelf life. Besides, the sensory scores of salmon samples were also significantly improved. In general, PDT not only has a positive effect on organoleptic indicators but is also a potential antimicrobial strategy for improving the quality of salmon sashimi.

An Analysis of the Gene Expression Associated with Lymph Node Metastasis in Colorectal Cancer.

Objective: This study aimed to explore the genes regulating lymph node metastasis in colorectal cancer (CRC) and to clarify their relationship with tumor immune cell infiltration and patient prognoses. Methods: The data sets of CRC patients were collected through the Cancer Gene Atlas database; the differentially expressed genes (DEGs) associated with CRC lymph node metastasis were screened; a protein-protein interaction (PPI) network was constructed; the top 20 hub genes were selected; the Gene Ontology functions and the Kyoto Encyclopedia of Genes and Genomes pathways were enriched and analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to further screen the characteristic genes associated with CRC lymph node metastasis in 20 hub genes, exploring the correlation between the characteristic genes and immune cell infiltration, conducting a univariate COX analysis on the characteristic genes, obtaining survival-related genes, constructing a risk score formula, conducting a Kaplan-Meier analysis based on the risk score formula, and performing a multivariate COX regression analysis on the clinical factors and risk scores. Results: A total of 62 DEGs associated with CRC lymph node metastasis were obtained. Among the 20 hub genes identified via PPI, only calcium-activated chloride channel regulator 1 (CLCA1) expression was down-regulated in lymph node metastasis, and the rest were up-regulated. A total of nine characteristic genes associated with CRC lymph node metastasis (KIF1A, TMEM59L, CLCA1, COL9A3, GDF5, TUBB2B, STMN2, FOXN1, and SCN5A) were screened using the LASSO regression method. The nine characteristic genes were significantly related to different kinds of immune cell infiltration, from which three survival-related genes (TMEM59L, CLCA1, and TUBB2B) were screened. A multi-factor COX regression showed that the risk scores obtained from TMEM59L, CLCA1, and TUBB2B were independent prognostic factors. Immunohistochemical validation was performed in tissue samples from patients with rectal and colon cancer. Conclusion: TMEM59L, CLCA1, and TUBB2B were independent prognostic factors associated with lymphatic metastasis of CRC.

Comparison of proanthocyanidins A2 and B2 on IgE-reactivity and epitopes in Gly m 6 using multispectral, LC/MS-MS and molecular docking.

This study comparatively analyzed the changes in IgE-reactivity and epitopes in proanthocyanidins A2- (PA-Gly m 6) and B2-Gly m 6 (PB-Gly m 6) conjugates prepared by alkali treatment at 80 °C for 20 min. Similar to the western blot, ELISA also showed a higher reduced IgE-reactivity in PA-Gly m 6 (70.12 %) than PB-Gly m 6 (63.17 %). SDS-PAGE demonstrated that proanthocyanidins A2 caused more formation of >180 kDa polymers than proanthocyanidins B2. Multispectral analyses revealed that PA-Gly m 6 exhibited more structural alteration (e.g., a decrease of α-helical content and ANS fluorescence intensity) to unfold protein structure than proanthocyanidins B2, improving the accessibility to modify Gly m 6 for shielding or destroying conformational epitopes. LC/MS-MS revealed that PA-Gly m 6 conjugates had a lower abundance of allergens, peptides and linear epitopes than PB-Gly m 6 conjugates. Molecular docking showed that proanthocyanidins A2 and B2 reacted with Gln-317 and Asn-94 of epitopes, respectively. Overall, proanthocyanidins A2 is more effective than proanthocyanidins B2 to decrease the IgE-reactivity of Gly m 6 due to more shielding or destruction of conformational epitopes and lower content allergens and linear epitopes, which was attributed to more protein-crosslinks formation and structural changes in PA-Gly m 6 conjugates.

Downregulation of miR­7 and miR­153 is involved in Helicobacter pylori CagA induced gastric carcinogenesis and progression.

Helicobacter pylori (H. pylori) infection plays a pivotal role in the development of gastric cancer (GC). However, the association between aberrant microRNAs (miRNAs/miRs) expression and H. pylori­induced GC remains poorly understood. The present study reported that repeated infection of H. pylori caused the oncogenicity of GES­1 cells in BALB/c Nude mice. miRNA sequencing revealed that both miR­7 and miR­153 were significantly decreased in the cytotoxin­associated gene A (CagA) positive GC tissues and this was further confirmed in a chronic infection model of GES­1/HP cells. Further biological function experiments and in vivo experiments validated that miR­7 and miR­153 can promote apoptosis and autophagy, inhibit proliferation and inflammatory response in GES­1/HP cells. All the associations between miR­7/miR­153 and their potential targets were revealed via bioinformatics prediction and dual­luciferase reporter assay. Particularly, downregulation of both miR­7 and miR­153 obtained an improved sensitivity and specificity in diagnosing H. pylori (CagA+)­induced GC. The present study identified that the combination of miR­7 and miR­153 may be regarded as novel therapeutic targets in H. pylori CagA (+)­associated GC.

Effect of homogenization on lipid profiling in Saanen goat milk based on UHPLC-QTOF-MS lipidomics.

Homogenization might change the lipid composition of goat milk. This study aimed to investigate the lipid profiles, and identify different lipids (DLs) of raw goat milk (RGM) and homogenized goat milk (HGM) using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and multivariate statistics. Fifty-six DLs (VIP ≥ 1 and |Log2FC| ≥ 1.0) were identified from 1057 lipids assigned to 29 subclasses in RGM and HGM. Notably, there were many phosphatidylcholines (PCs) decreased after homogenization, while lysophosphatidylcholines (LPCs) were opposite. Our results provide more details on the impact of homogenization on goat milk lipids.

Investigation of the differences in the effect of (-)-epigallocatechin gallate and proanthocyanidins on the functionality and allergenicity of soybean protein isolate.

In this study, the differences in effects of (-)-epigallocatechin gallate (EGCG) and proanthocyanidins (PC) on the functionality and allergenicity of soybean protein isolate (SPI) were studied. SDS-PAGE demonstrated that SPI-PC conjugates exhibited more high-molecular-weight polymers (>180 kDa) than SPI-EGCG conjugates. Structural analysis showed that SPI-PC conjugates exhibited more disordered structures and protein-unfolding, improving the accessibility of PC to modify SPI, compared to SPI-EGCG conjugates. LC/MS-MS demonstrated that PC caused more modification of SPI and major soybean allergens than EGCG, resulting in a lower abundance of epitopes. The successful attachment of EGCG and PC to SPI significantly increased antioxidant capacity in conjugates. Furthermore, SPI-PC conjugates exhibited greater emulsifying activity and lower immunoglobulin E (IgE) binding capacity than SPI-EGCG conjugates, which was attributed to more disordered structure and protein-unfolding in SPI-PC conjugates. It is implied that proanthocyanidins may be promising compounds to interact with soybean proteins to produce functional and hypoallergenic foods.

The alteration of composition, conformation, IgE-reactivity and functional attributes in proanthocyanidins-soy protein 7S conjugates formed by alkali-heating treatment: Multi-spectroscopic and proteomic analyses.

This study assessed the alteration of IgE-reactivity and functional attribute in soy protein 7S-proanthocyanidins conjugates (7S-80PC) formed by alkali-heating treatment (pH 9.0, 80 °C, 20 min). SDS-PAGE demonstrated that 7S-80PC exhibited the formation of >180 kDa polymers, although the heated 7S (7S-80) had no changes. Multispectral experiments revealed more protein unfolding in 7S-80PC than in 7S-80. Heatmap analysis showed that 7S-80PC showed more alteration of protein, peptide and epitope profiles than 7S-80. LC/MS-MS demonstrated that the content of total dominant linear epitopes was increased by 11.4 % in 7S-80, but decreased by 47.4 % in 7S-80PC. As a result, Western-blot and ELISA showed that 7S-80PC exhibited lower IgE-reactivity than 7S-80, probably because 7S-80PC exhibited more protein-unfolding to increase the accessibility of proanthocyanidins to mask and destroy the exposed conformational epitopes and dominant linear epitopes induced by heating treatment. Furthermore, the successful attachment of PC to soy 7S protein significantly increased antioxidant activity in 7S-80PC. 7S-80PC also showed higher emulsion activity than 7S-80 owing to its high protein flexibility and protein unfolding. However, 7S-80PC exhibited lower foaming properties than 7S-80. Therefore, the addition of proanthocyanidins could decrease IgE-reactivity and alter the functional attribute of the heated soy 7S protein.

Multi-spectral and proteomic insights into the impact of proanthocyanidins on IgE binding capacity and functionality in soy 11S protein during alkali-heating treatment.

This study evaluated the impact of proanthocyanidins on immunoglobulin E (IgE) binding capacity, antioxidant, foaming and emulsifying properties in soy 11S protein following alkali treatment at 80 °C for 20 min. The formation of >180 kDa polymer was observed in the combined heating and proanthocyanidins-conjugation treatment sample (11S-80PC) rather than in the heating treated sample (11S-80) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The structural analyzes demonstrated that 11S-80PC exhibited more protein unfolding than 11S-80. Heatmap analysis revealed that 11S-80PC had more alteration of peptide and epitope profiles in 11S than in 11S-80. Molecular docking showed that PC could well react with soy protein 11S. Liquid chromatography tandem MS analysis (LC/MS-MS) demonstrated that there was a 35.6 % increase in 11S-80, but a 14.5 % decrease in 11S-80PC for the abundance of total linear epitopes. As a result, 11S-80PC exhibited more reduction in IgE binding capacities than 11S-80 owing to more obscuring and disruption of linear and conformational epitopes induced by structural changes. Moreover, 11S-80PC exhibited higher antioxidant capacities, foaming properties and emulsifying activity than 11S-80. Therefore, the addition of proanthocyanidins could decrease allergenic activity and enhance the functional properties of the heated soy 11S protein.

Effect of proanthocyanidins on protein composition, conformational structure, IgE binding capacities and functional properties in soybean protein.

This study was performed to determine the crosslinking formed by proanthocyanidins (PC) with respect to IgE binding capacities, functionality, structure and composition of soybean protein (SPI) following the alkali treatment at 60-100 °C. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed the formation of >180 kDa polymers, resulting from the formation of SPI-PC conjugates and protein cross-links. Structural analyses demonstrated that SPI-PC conjugates exhibited structural changes to unfold proteins and increase molecular flexibility. Liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS) showed a decrease in unique protein and peptide numbers as well as major allergen and dominant epitopes abundance. When SPI was treated with PC under the alkali treatment at 80 °C, it exhibited a maximum reduction (68.8 %) in the immunoglobulin E (IgE) binding capacity and a maximum increase in DPPH radical scavenging activities (6.11-fold), ABTS + radical scavenging activities (4.80-fold), foaming stability (6.1 %) and emulsifying activity (27.3 %), compared to the control SPI. Overall, this study demonstrates that alkali treatment at 60-100 °C to form SPI-PC conjugates has potential applications for producing hypoallergenic soybean products with the desired functionality, most especially from alkali treatment at 80 °C. Moreover, the addition of PC pronouncedly alleviates the undesirable functional properties in heated SPI.

Heat-induced changes in epitopes and IgE binding capacity of soybean protein isolate.

The effects of heating temperature on epitopes, IgE-binding capacity, and conformation of soybean protein isolate (SPI) were investigated in this study. Indirect ELISA demonstrated that the IgE binding capacity of SPI was increased by 13.1 %-31.6 % after being heated at 60-100 °C for 20 min. SDS-PAGE demonstrated no changes in protein profiles, and native PAGE revealed the formation of aggregates. Structural analyses demonstrated the protein unfolding, appearing temperature-dependent, thus exposing conformational epitopes. Peptide mapping analysis revealed the changes in peptide profiles of major allergens (Gly m 4, Gly m 5, Gly m 6, P28, and Kunitz trypsin inhibitor). LC/MS-MS demonstrated that heating caused the masking or exposure of linear epitopes in Gly m 4 - Gly m 6 and P28. Therefore, heating caused structural changes to expose epitopes to increase IgE binding capacity in SPI. Patients with soybean allergy should avoid the heated SPI until the results of clinical trials are confirmed.

Protein modification, IgE binding capacity, and functional properties of soybean protein upon conjugation with polyphenols.

The modification, structure, functionality and IgE binding capacity of soybean protein (SPI) upon covalent conjugation with gallic acid (GA), caffeic acid (CA), and tannic acid (TA) under alkali treatment were assessed. SDS-PAGE showed the formation of SPI-polyphenol conjugates and the cross-linking of SPI. Protein unfolding in the conjugates was observed, characterized by a reduction in α-helix and an increase in UV ultraviolet absorption, surface hydrophobicity and free sulfhydryl groups. LC/MS-MS demonstrated that the modification of protein and major allergens varied with the types of polyphenols. Western-blot and ELISA demonstrated that SPI-polyphenol conjugates exhibited a significant reduced IgE binding capacity due to the masking or destruction of epitopes among Gly m 4, Gly m 5, Gly m 6 and P28, resulting from structural changes. Additionally, antioxidant capacity and emulsifying properties were increased in SPI-polyphenol conjugates. Therefore, polyphenol treatment may be a promising method to prepare hypoallergenic soybean products with desired functionality.

Sesame allergy: mechanisms, prevalence, allergens, residue detection, effects of processing and cross-reactivity.

Sesame allergy is a serious public health problem and is mainly induced by IgE-mediated reactions, whose prevalence is distributed all over the world. Sesame has been included on the priority allergic food list in many countries. This review summarizes the mechanism and prevalence of sesame allergy. The characteristics, structures and epitopes of sesame allergens (Ses i 1 to Ses i 7) are included. Moreover, the detection methods for sesame allergens are evaluated, including nucleic-acid, immunoassays, mass spectrometry, and biosensors. Various processing techniques for reducing sesame allergenicity are discussed. Additionally, the potential cross-reactivity of sesame with other plant foods is assessed. It is found that the allergenicity of sesame is related to the structures and epitopes of sesame allergens. Immunoassays and mass spectrometry are the major analytical tools for detecting and quantifying sesame allergens in food. Limited technologies have been successfully used to reduce the antigenicity of sesame, involving microwave heating, high hydrostatic pressure, salt and pH treatment. More technologies for reducing the allergenicity of sesame should be widely investigated in future studies. The reduction of allergenicity in processed sesames should be ultimately confirmed by clinical studies. What's more, sesame may exhibit cross-reactivity with peanut and tree nuts.

Structure and gene cluster of the O-antigen of Enterobacter cloacae G2559.

The O-polysaccharide (OPS) was isolated by mild acid degradation of the lipopolysaccharide of Enterobacter cloacae G2559 and studied by sugar analysis along with 1D and 2D 1H and 13C NMR spectroscopy. The following structure of the branched pentasaccharide repeating unit was established. The O-antigen gene cluster of Enterobacter cloacae G2559 was sequenced. The gene functions were tentatively assigned by comparison with sequences in the available databases and found to be in full agreement with the O-antigen structure.

Characterization of the O-antigen gene clusters and development of a molecular serotyping method for Vibrio fluvialis.

Vibrio fluvialis is an emerging foodborne pathogen that causes severe infections. Serotyping based on surface polysaccharide antigens is important for the clinical detection and epidemiological surveillance of pathogens such as V. fluvialis. For example, variation of the O-antigen, which is highly polymorphic and is responsible for the majority of antigenic variability on the bacterial cell surface, provides the basis for serotyping of Gram-negative bacteria. Currently, there has been no analysis of the O-antigen gene clusters in V. fluvialis. In this study, the putative O-antigen gene clusters of 18 V. fluvialis serogroups (O1-O18), which exhibit a high level diversity, were analyzed by whole-genome sequencing. A microsphere-based suspension array (MSA) based on O-serogroup-specific genes was developed for identification of V. fluvialis strains O1-O18 and evaluated for specificity and sensitivity in double-blind tests. Furthermore, analysis of 62 publicly available V. fluvialis genomes identified 13 new O-antigen gene cluster types. The detection sensitivity was determined to be 10-2 ng for genomic DNA and 103 CFU for pure cultures. When testing simulated samples in an oyster background, 2 to 20 CFU per gram inoculated could be detected after enrichment using this method. Our work provides an efficient tool for rapid detection and identification of V. fluvialis serogroups from clinical and environmental samples, with the potential for use in epidemiological investigations and food safety applications.

The complete mitogenome of Chrysopogon zizanioides (L.) Roberty (Poaceae), with its phylogenetic analysis.

Vetiver grass (Chrysopogon zizanioides), is a perennial and tussock C4 grass from the genus Chrysopogon of Poaceae, which has been widely used as a natural and inexpensive resource for multifarious environmental applications. The complete mitogenome of C. zizanioides was 551,622 bp in length, containing 40 protein-coding genes (PCGs), 19 transfer RNA genes (tRNAs), and six ribosomal RNA genes (rRNAs). All PCGs started with ATG and stopped with TNN (TAA, TAG, and TGA). The overall nucleotide composition is: 28.2% A, 28.2% T, 21.7% G, and 21.9% C, with a biased A + T content of 56.4%. Phylogenetic analysis using 14 PCGs of 22 species showed that C. zizanioides display a close relationship with Saccharum officinarum (LC107874) and Sorghum bicolor (DQ984518) in Poaceae.

The Fecal Microbiota Transplantation: A Remarkable Clinical Therapy for Slow Transit Constipation in Future.

Slow transit constipation is a common condition that would be difficult to treat in clinical practice with a widespread incidence in the population. Pharmacotherapy and surgery are common treatment modalities. However, the clinical effect is limited, and patients still suffer from it. As the researchers strived in this field for decades, the profound relationship between slow transit constipation and fecal microbiota transplantation has comprehensively been sustained. It is very pivotal to maintain intestinal homeostasis, the structure function and metabolic function of symbiotic bacteria, which can inhibit the engraftment of intestinal pathogens. This mini review explains the treatment effects and possible mechanisms of the fecal microbiota transplantation in treating slow transit constipation. Simultaneously, it is found that there is significant improvement in the disease by adjusting the intestinal microbes like fecal microbiota transplantation. Fecal microbiota transplantation has efficient therapeutic effects in slow transit constipation compared with traditional therapies.