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1.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38904542

RESUMO

The inherent heterogeneity of cancer contributes to highly variable responses to any anticancer treatments. This underscores the need to first identify precise biomarkers through complex multi-omics datasets that are now available. Although much research has focused on this aspect, identifying biomarkers associated with distinct drug responders still remains a major challenge. Here, we develop MOMLIN, a multi-modal and -omics machine learning integration framework, to enhance drug-response prediction. MOMLIN jointly utilizes sparse correlation algorithms and class-specific feature selection algorithms, which identifies multi-modal and -omics-associated interpretable components. MOMLIN was applied to 147 patients' breast cancer datasets (clinical, mutation, gene expression, tumor microenvironment cells and molecular pathways) to analyze drug-response class predictions for non-responders and variable responders. Notably, MOMLIN achieves an average AUC of 0.989, which is at least 10% greater when compared with current state-of-the-art (data integration analysis for biomarker discovery using latent components, multi-omics factor analysis, sparse canonical correlation analysis). Moreover, MOMLIN not only detects known individual biomarkers such as genes at mutation/expression level, most importantly, it correlates multi-modal and -omics network biomarkers for each response class. For example, an interaction between ER-negative-HMCN1-COL5A1 mutations-FBXO2-CSF3R expression-CD8 emerge as a multimodal biomarker for responders, potentially affecting antimicrobial peptides and FLT3 signaling pathways. In contrast, for resistance cases, a distinct combination of lymph node-TP53 mutation-PON3-ENSG00000261116 lncRNA expression-HLA-E-T-cell exclusions emerged as multimodal biomarkers, possibly impacting neurotransmitter release cycle pathway. MOMLIN, therefore, is expected advance precision medicine, such as to detect context-specific multi-omics network biomarkers and better predict drug-response classifications.


Assuntos
Neoplasias da Mama , Aprendizado de Máquina , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Algoritmos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Biologia Computacional/métodos , Genômica/métodos
2.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-39007595

RESUMO

Biomedical research now commonly integrates diverse data types or views from the same individuals to better understand the pathobiology of complex diseases, but the challenge lies in meaningfully integrating these diverse views. Existing methods often require the same type of data from all views (cross-sectional data only or longitudinal data only) or do not consider any class outcome in the integration method, which presents limitations. To overcome these limitations, we have developed a pipeline that harnesses the power of statistical and deep learning methods to integrate cross-sectional and longitudinal data from multiple sources. In addition, it identifies key variables that contribute to the association between views and the separation between classes, providing deeper biological insights. This pipeline includes variable selection/ranking using linear and nonlinear methods, feature extraction using functional principal component analysis and Euler characteristics, and joint integration and classification using dense feed-forward networks for cross-sectional data and recurrent neural networks for longitudinal data. We applied this pipeline to cross-sectional and longitudinal multiomics data (metagenomics, transcriptomics and metabolomics) from an inflammatory bowel disease (IBD) study and identified microbial pathways, metabolites and genes that discriminate by IBD status, providing information on the etiology of IBD. We conducted simulations to compare the two feature extraction methods.


Assuntos
Aprendizado Profundo , Doenças Inflamatórias Intestinais , Humanos , Estudos Transversais , Doenças Inflamatórias Intestinais/classificação , Doenças Inflamatórias Intestinais/genética , Estudos Longitudinais , Análise Discriminante , Metabolômica/métodos , Biologia Computacional/métodos
3.
Brief Bioinform ; 25(Supplement_1)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39101486

RESUMO

Multi-omics (genomics, transcriptomics, epigenomics, proteomics, metabolomics, etc.) research approaches are vital for understanding the hierarchical complexity of human biology and have proven to be extremely valuable in cancer research and precision medicine. Emerging scientific advances in recent years have made high-throughput genome-wide sequencing a central focus in molecular research by allowing for the collective analysis of various kinds of molecular biological data from different types of specimens in a single tissue or even at the level of a single cell. Additionally, with the help of improved computational resources and data mining, researchers are able to integrate data from different multi-omics regimes to identify new prognostic, diagnostic, or predictive biomarkers, uncover novel therapeutic targets, and develop more personalized treatment protocols for patients. For the research community to parse the scientifically and clinically meaningful information out of all the biological data being generated each day more efficiently with less wasted resources, being familiar with and comfortable using advanced analytical tools, such as Google Cloud Platform becomes imperative. This project is an interdisciplinary, cross-organizational effort to provide a guided learning module for integrating transcriptomics and epigenetics data analysis protocols into a comprehensive analysis pipeline for users to implement in their own work, utilizing the cloud computing infrastructure on Google Cloud. The learning module consists of three submodules that guide the user through tutorial examples that illustrate the analysis of RNA-sequence and Reduced-Representation Bisulfite Sequencing data. The examples are in the form of breast cancer case studies, and the data sets were procured from the public repository Gene Expression Omnibus. The first submodule is devoted to transcriptomics analysis with the RNA sequencing data, the second submodule focuses on epigenetics analysis using the DNA methylation data, and the third submodule integrates the two methods for a deeper biological understanding. The modules begin with data collection and preprocessing, with further downstream analysis performed in a Vertex AI Jupyter notebook instance with an R kernel. Analysis results are returned to Google Cloud buckets for storage and visualization, removing the computational strain from local resources. The final product is a start-to-finish tutorial for the researchers with limited experience in multi-omics to integrate transcriptomics and epigenetics data analysis into a comprehensive pipeline to perform their own biological research.This manuscript describes the development of a resource module that is part of a learning platform named ``NIGMS Sandbox for Cloud-based Learning'' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox [16] at the beginning of this Supplement. This module delivers learning materials on the analysis of bulk and single-cell ATAC-seq data in an interactive format that uses appropriate cloud resources for data access and analyses.


Assuntos
Computação em Nuvem , Epigenômica , Humanos , Epigenômica/métodos , Epigênese Genética , Transcriptoma , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Software , Mineração de Dados/métodos
4.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37670505

RESUMO

A key problem in systems biology is the discovery of regulatory mechanisms that drive phenotypic behaviour of complex biological systems in the form of multi-level networks. Modern multi-omics profiling techniques probe these fundamental regulatory networks but are often hampered by experimental restrictions leading to missing data or partially measured omics types for subsets of individuals due to cost restrictions. In such scenarios, in which missing data is present, classical computational approaches to infer regulatory networks are limited. In recent years, approaches have been proposed to infer sparse regression models in the presence of missing information. Nevertheless, these methods have not been adopted for regulatory network inference yet. In this study, we integrated regression-based methods that can handle missingness into KiMONo, a Knowledge guided Multi-Omics Network inference approach, and benchmarked their performance on commonly encountered missing data scenarios in single- and multi-omics studies. Overall, two-step approaches that explicitly handle missingness performed best for a wide range of random- and block-missingness scenarios on imbalanced omics-layers dimensions, while methods implicitly handling missingness performed best on balanced omics-layers dimensions. Our results show that robust multi-omics network inference in the presence of missing data with KiMONo is feasible and thus allows users to leverage available multi-omics data to its full extent.


Assuntos
Benchmarking , Multiômica , Humanos , Biologia de Sistemas
5.
Brief Bioinform ; 24(5)2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37594302

RESUMO

The availability of high-throughput sequencing data creates opportunities to comprehensively understand human diseases as well as challenges to train machine learning models using such high dimensions of data. Here, we propose a denoised multi-omics integration framework, which contains a distribution-based feature denoising algorithm, Feature Selection with Distribution (FSD), for dimension reduction and a multi-omics integration framework, Attention Multi-Omics Integration (AttentionMOI) to predict cancer prognosis and identify cancer subtypes. We demonstrated that FSD improved model performance either using single omic data or multi-omics data in 15 The Cancer Genome Atlas Program (TCGA) cancers for survival prediction and kidney cancer subtype identification. And our integration framework AttentionMOI outperformed machine learning models and current multi-omics integration algorithms with high dimensions of features. Furthermore, FSD identified features that were associated to cancer prognosis and could be considered as biomarkers.


Assuntos
Genômica , Neoplasias , Humanos , Genômica/métodos , Multiômica , Neoplasias/genética , Algoritmos
6.
Brief Bioinform ; 25(1)2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-38205966

RESUMO

Multi-omics data integration is a complex and challenging task in biomedical research. Consensus clustering, also known as meta-clustering or cluster ensembles, has become an increasingly popular downstream tool for phenotyping and endotyping using multiple omics and clinical data. However, current consensus clustering methods typically rely on ensembling clustering outputs with similar sample coverages (mathematical replicates), which may not reflect real-world data with varying sample coverages (biological replicates). To address this issue, we propose a new consensus clustering with missing labels (ccml) strategy termed ccml, an R protocol for two-step consensus clustering that can handle unequal missing labels (i.e. multiple predictive labels with different sample coverages). Initially, the regular consensus weights are adjusted (normalized) by sample coverage, then a regular consensus clustering is performed to predict the optimal final cluster. We applied the ccml method to predict molecularly distinct groups based on 9-omics integration in the Karolinska COSMIC cohort, which investigates chronic obstructive pulmonary disease, and 24-omics handprint integrative subgrouping of adult asthma patients of the U-BIOPRED cohort. We propose ccml as a downstream toolkit for multi-omics integration analysis algorithms such as Similarity Network Fusion and robust clustering of clinical data to overcome the limitations posed by missing data, which is inevitable in human cohorts consisting of multiple data modalities. The ccml tool is available in the R language (https://CRAN.R-project.org/package=ccml, https://github.com/pulmonomics-lab/ccml, or https://github.com/ZhoulabCPH/ccml).


Assuntos
Asma , Multiômica , Adulto , Humanos , Consenso , Análise por Conglomerados , Algoritmos , Asma/genética
7.
Brief Bioinform ; 24(1)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36583521

RESUMO

Bulk sequencing experiments (single- and multi-omics) are essential for exploring wide-ranging biological questions. To facilitate interactive, exploratory tasks, coupled with the sharing of easily accessible information, we present bulkAnalyseR, a package integrating state-of-the-art approaches using an expression matrix as the starting point (pre-processing functions are available as part of the package). Static summary images are replaced with interactive panels illustrating quality-checking, differential expression analysis (with noise detection) and biological interpretation (enrichment analyses, identification of expression patterns, followed by inference and comparison of regulatory interactions). bulkAnalyseR can handle different modalities, facilitating robust integration and comparison of cis-, trans- and customised regulatory networks.


Assuntos
Multiômica
8.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36715269

RESUMO

Predicting therapeutic responses in cancer patients is a major challenge in the field of precision medicine due to high inter- and intra-tumor heterogeneity. Most drug response models need to be improved in terms of accuracy, and there is limited research to assess therapeutic responses of particular tumor types. Here, we developed a novel method DROEG (Drug Response based on Omics and Essential Genes) for prediction of drug response in tumor cell lines by integrating genomic, transcriptomic and methylomic data along with CRISPR essential genes, and revealed that the incorporation of tumor proliferation essential genes can improve drug sensitivity prediction. Concisely, DROEG integrates literature-based and statistics-based methods to select features and uses Support Vector Regression for model construction. We demonstrate that DROEG outperforms most state-of-the-art algorithms by both qualitative (prediction accuracy for drug-sensitive/resistant) and quantitative (Pearson correlation coefficient between the predicted and actual IC50) evaluation in Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopedia datasets. In addition, DROEG is further applied to the pan-gastrointestinal tumor with high prevalence and mortality as a case study at both cell line and clinical levels to evaluate the model efficacy and discover potential prognostic biomarkers in Cisplatin and Epirubicin treatment. Interestingly, the CRISPR essential gene information is found to be the most important contributor to enhance the accuracy of the DROEG model. To our knowledge, this is the first study to integrate essential genes with multi-omics data to improve cancer drug response prediction and provide insights into personalized precision treatment.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Genes Essenciais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Genômica/métodos , Medicina de Precisão/métodos
9.
BMC Bioinformatics ; 25(1): 27, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225583

RESUMO

BACKGROUND: The recent development of high-throughput sequencing has created a large collection of multi-omics data, which enables researchers to better investigate cancer molecular profiles and cancer taxonomy based on molecular subtypes. Integrating multi-omics data has been proven to be effective for building more precise classification models. Most current multi-omics integrative models use either an early fusion in the form of concatenation or late fusion with a separate feature extractor for each omic, which are mainly based on deep neural networks. Due to the nature of biological systems, graphs are a better structural representation of bio-medical data. Although few graph neural network (GNN) based multi-omics integrative methods have been proposed, they suffer from three common disadvantages. One is most of them use only one type of connection, either inter-omics or intra-omic connection; second, they only consider one kind of GNN layer, either graph convolution network (GCN) or graph attention network (GAT); and third, most of these methods have not been tested on a more complex classification task, such as cancer molecular subtypes. RESULTS: In this study, we propose a novel end-to-end multi-omics GNN framework for accurate and robust cancer subtype classification. The proposed model utilizes multi-omics data in the form of heterogeneous multi-layer graphs, which combine both inter-omics and intra-omic connections from established biological knowledge. The proposed model incorporates learned graph features and global genome features for accurate classification. We tested the proposed model on the Cancer Genome Atlas (TCGA) Pan-cancer dataset and TCGA breast invasive carcinoma (BRCA) dataset for molecular subtype and cancer subtype classification, respectively. The proposed model shows superior performance compared to four current state-of-the-art baseline models in terms of accuracy, F1 score, precision, and recall. The comparative analysis of GAT-based models and GCN-based models reveals that GAT-based models are preferred for smaller graphs with less information and GCN-based models are preferred for larger graphs with extra information.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias , Conhecimento , Aprendizagem , Redes Neurais de Computação , Neoplasias/genética
10.
BMC Genomics ; 25(1): 267, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468234

RESUMO

In every omics experiment, genes or their products are identified for which even state of the art tools are unable to assign a function. In the biotechnology chassis organism Pseudomonas putida, these proteins of unknown function make up 14% of the proteome. This missing information can bias analyses since these proteins can carry out functions which impact the engineering of organisms. As a consequence of predicting protein function across all organisms, function prediction tools generally fail to use all of the types of data available for any specific organism, including protein and transcript expression information. Additionally, the release of Alphafold predictions for all Uniprot proteins provides a novel opportunity for leveraging structural information. We constructed a bespoke machine learning model to predict the function of recalcitrant proteins of unknown function in Pseudomonas putida based on these sources of data, which annotated 1079 terms to 213 proteins. Among the predicted functions supplied by the model, we found evidence for a significant overrepresentation of nitrogen metabolism and macromolecule processing proteins. These findings were corroborated by manual analyses of selected proteins which identified, among others, a functionally unannotated operon that likely encodes a branch of the shikimate pathway.


Assuntos
Pseudomonas putida , Pseudomonas putida/genética , Proteoma/metabolismo , Multiômica , Biotecnologia , Óperon
11.
Brief Bioinform ; 23(6)2022 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-36252928

RESUMO

Pathway analysis has been widely used to detect pathways and functions associated with complex disease phenotypes. The proliferation of this approach is due to better interpretability of its results and its higher statistical power compared with the gene-level statistics. A plethora of pathway analysis methods that utilize multi-omics setup, rather than just transcriptomics or proteomics, have recently been developed to discover novel pathways and biomarkers. Since multi-omics gives multiple views into the same problem, different approaches are employed in aggregating these views into a comprehensive biological context. As a result, a variety of novel hypotheses regarding disease ideation and treatment targets can be formulated. In this article, we review 32 such pathway analysis methods developed for multi-omics and multi-cohort data. We discuss their availability and implementation, assumptions, supported omics types and databases, pathway analysis techniques and integration strategies. A comprehensive assessment of each method's practicality, and a thorough discussion of the strengths and drawbacks of each technique will be provided. The main objective of this survey is to provide a thorough examination of existing methods to assist potential users and researchers in selecting suitable tools for their data and analysis purposes, while highlighting outstanding challenges in the field that remain to be addressed for future development.


Assuntos
Genômica , Proteômica , Genômica/métodos , Transcriptoma , Biomarcadores
12.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34607358

RESUMO

The discovery of cancer subtypes has become much-researched topic in oncology. Dividing cancer patients into subtypes can provide personalized treatments for heterogeneous patients. High-throughput technologies provide multiple omics data for cancer subtyping. Integration of multi-view data is used to identify cancer subtypes in many computational methods, which obtain different subtypes for the same cancer, even using the same multi-omics data. To a certain extent, these subtypes from distinct methods are related, which may have certain guiding significance for cancer subtyping. It is a challenge to effectively utilize the valuable information of distinct subtypes to produce more accurate and reliable subtypes. A weighted ensemble sparse latent representation (subtype-WESLR) is proposed to detect cancer subtypes on heterogeneous omics data. Using a weighted ensemble strategy to fuse base clustering obtained by distinct methods as prior knowledge, subtype-WESLR projects each sample feature profile from each data type to a common latent subspace while maintaining the local structure of the original sample feature space and consistency with the weighted ensemble and optimizes the common subspace by an iterative method to identify cancer subtypes. We conduct experiments on various synthetic datasets and eight public multi-view datasets from The Cancer Genome Atlas. The results demonstrate that subtype-WESLR is better than competing methods by utilizing the integration of base clustering of exist methods for more precise subtypes.


Assuntos
Algoritmos , Neoplasias , Análise por Conglomerados , Humanos , Neoplasias/genética
13.
FASEB J ; 37(7): e23056, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37342921

RESUMO

Revealing the key genes involved in polycystic ovary syndrome (PCOS) and elucidating its pathogenic mechanism is of extreme importance for the development of targeted clinical therapy for PCOS. Investigating disease by integrating several associated and interacting molecules in biological systems will make it possible to discover new pathogenic genes. In this study, an integrative disease-associated molecule network, combining protein-protein interactions and protein-metabolites interactions (PPMI) network was constructed based on the PCOS-associated genes and metabolites systematically collected. This new PPMI strategy identified several potential PCOS-associated genes, which have unreported in previous publications. Moreover, the systematic analysis of five benchmarks data sets indicated the DERL1 was identified as downregulated in PCOS granulosa cell and has good classification performance between PCOS patients and healthy controls. CCR2 and DVL3 were upregulated in PCOS adipose tissues and have good classification performance. The expression of novel gene FXR2 identified in this study is significantly increased in ovarian granulosa cells of PCOS patients compared with controls via quantitative analysis. Our study uncovers substantial differences in the PCOS-specific tissue and provides a plethora of information on dysregulated genes and metabolites that are linked to PCOS. This knowledgebase could have the potential to benefit the scientific and clinical community. In sum, the identification of novel gene associated with PCOS provides valuable insights into the underlying molecular mechanisms of PCOS and could potentially lead to the development of new diagnostic and therapeutic strategies.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/metabolismo , Células da Granulosa/metabolismo
14.
Stat Med ; 43(5): 983-1002, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38146838

RESUMO

With the growing commonality of multi-omics datasets, there is now increasing evidence that integrated omics profiles lead to more efficient discovery of clinically actionable biomarkers that enable better disease outcome prediction and patient stratification. Several methods exist to perform host phenotype prediction from cross-sectional, single-omics data modalities but decentralized frameworks that jointly analyze multiple time-dependent omics data to highlight the integrative and dynamic impact of repeatedly measured biomarkers are currently limited. In this article, we propose a novel Bayesian ensemble method to consolidate prediction by combining information across several longitudinal and cross-sectional omics data layers. Unlike existing frequentist paradigms, our approach enables uncertainty quantification in prediction as well as interval estimation for a variety of quantities of interest based on posterior summaries. We apply our method to four published multi-omics datasets and demonstrate that it recapitulates known biology in addition to providing novel insights while also outperforming existing methods in estimation, prediction, and uncertainty quantification. Our open-source software is publicly available at https://github.com/himelmallick/IntegratedLearner.


Assuntos
Multiômica , Software , Humanos , Teorema de Bayes , Estudos Transversais , Biomarcadores
15.
BMC Med Res Methodol ; 24(1): 168, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095705

RESUMO

BACKGROUND: Understanding the complex interactions between genes and their causal effects on diseases is crucial for developing targeted treatments and gaining insight into biological mechanisms. However, the analysis of molecular networks, especially in the context of high-dimensional data, presents significant challenges. METHODS: This study introduces MRdualPC, a computationally tractable algorithm based on the MRPC approach, to infer large-scale causal molecular networks. We apply MRdualPC to investigate the upstream causal transcriptomics influencing hypertension using a comprehensive dataset of kidney genome and transcriptome data. RESULTS: Our algorithm proves to be 100 times faster than MRPC on average in identifying transcriptomics drivers of hypertension. Through clustering, we identify 63 modules with causal driver genes, including 17 modules with extensive causal networks. Notably, we find that genes within one of the causal networks are associated with the electron transport chain and oxidative phosphorylation, previously linked to hypertension. Moreover, the identified causal ancestor genes show an over-representation of blood pressure-related genes. CONCLUSIONS: MRdualPC has the potential for broader applications beyond gene expression data, including multi-omics integration. While there are limitations, such as the need for clustering in large gene expression datasets, our study represents a significant advancement in building causal molecular networks, offering researchers a valuable tool for analyzing big data and investigating complex diseases.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Hipertensão , Aprendizado de Máquina , Hipertensão/genética , Humanos , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Análise por Conglomerados
16.
Anim Biotechnol ; 35(1): 2331179, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38519440

RESUMO

Despite the significant threat of heat stress to livestock animals, only a few studies have considered the potential relationship between broiler chickens and their microbiota. Therefore, this study examined microbial modifications, transcriptional changes and host-microbiome interactions using a predicted metabolome data-based approach to understand the impact of heat stress on poultry. After the analysis, the host functional enrichment analysis revealed that pathways related to lipid and protein metabolism were elevated under heat stress conditions. In contrast, pathways related to the cell cycle were suppressed under normal environmental temperatures. In line with the transcriptome analysis, the microbial analysis results indicate that taxonomic changes affect lipid degradation. Heat stress engendered statistically significant difference in the abundance of 11 microorganisms, including Bacteroides and Peptostreptococcacea. Together, integrative approach analysis suggests that microbiota-induced metabolites affect host fatty acid peroxidation metabolism, which is correlated with the gene families of Acyl-CoA dehydrogenase long chain (ACADL), Acyl-CoA Oxidase (ACOX) and Acetyl-CoA Acyltransferase (ACAA). This integrated approach provides novel insights into heat stress problems and identifies potential biomarkers associated with heat stress.


Assuntos
Aves Domésticas , Transcriptoma , Animais , Aves Domésticas/genética , Aves Domésticas/metabolismo , Peroxidação de Lipídeos/genética , Jejuno/metabolismo , Galinhas/genética , Galinhas/metabolismo , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Lipídeos , Aminoácidos/genética , Aminoácidos/metabolismo
17.
Ecotoxicol Environ Saf ; 276: 116270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574645

RESUMO

Mycotoxin contamination has become a major food safety issue and greatly threatens human and animal health. Patulin (PAT), a common mycotoxin in the environment, is exposed through the food chain and damages the gastrointestinal tract. However, its mechanism of enterotoxicity at the genetic and metabolic levels remains to be elucidated. Herein, the intestinal histopathological and biochemical indices, transcriptome, and metabolome of C57BL/6 J mice exposed to different doses of PAT were successively assessed, as well as the toxicokinetics of PAT in vivo. The results showed that acute PAT exposure induced damaged villi and crypts, reduced mucus secretion, decreased SOD and GSH-Px activities, and enhanced MPO activity in the small intestine and mild damage in the colon. At the transcriptional level, the genes affected by PAT were dose-dependently altered in the small intestine and fluctuated in the colon. PAT primarily affected inflammation-related signaling pathways and oxidative phosphorylation in the small intestine and immune responses in the colon. At the metabolic level, amino acids decreased, and extensive lipids accumulated in the small intestine and colon. Seven metabolic pathways were jointly affected by PAT in two intestinal sites. Moreover, changes in PAT products and GST activity were detected in the small intestinal tissue but not in the colonic tissue, explaining the different damage degrees of the two sites. Finally, the integrated results collectively explained the toxicological mechanism of PAT, which damaged the small intestine directly and the colon indirectly. These results paint a clear panorama of intestinal changes after PAT exposure and provide valuable information on the exposure risk and toxic mechanism of PAT.


Assuntos
Metabolômica , Camundongos Endogâmicos C57BL , Patulina , Transcriptoma , Animais , Patulina/toxicidade , Camundongos , Transcriptoma/efeitos dos fármacos , Masculino , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Intestino Delgado/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia
18.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474033

RESUMO

Accurate cancer subtype prediction is crucial for personalized medicine. Integrating multi-omics data represents a viable approach to comprehending the intricate pathophysiology of complex diseases like cancer. Conventional machine learning techniques are not ideal for analyzing the complex interrelationships among different categories of omics data. Numerous models have been suggested using graph-based learning to uncover veiled representations and network formations unique to distinct types of omics data to heighten predictions regarding cancers and characterize patients' profiles, amongst other applications aimed at improving disease management in medical research. The existing graph-based state-of-the-art multi-omics integration approaches for cancer subtype prediction, MOGONET, and SUPREME, use a graph convolutional network (GCN), which fails to consider the level of importance of neighboring nodes on a particular node. To address this gap, we hypothesize that paying attention to each neighbor or providing appropriate weights to neighbors based on their importance might improve the cancer subtype prediction. The natural choice to determine the importance of each neighbor of a node in a graph is to explore the graph attention network (GAT). Here, we propose MOGAT, a novel multi-omics integration approach, leveraging GAT models that incorporate graph-based learning with an attention mechanism. MOGAT utilizes a multi-head attention mechanism to extract appropriate information for a specific sample by assigning unique attention coefficients to neighboring samples. Based on our knowledge, our group is the first to explore GAT in multi-omics integration for cancer subtype prediction. To evaluate the performance of MOGAT in predicting cancer subtypes, we explored two sets of breast cancer data from TCGA and METABRIC. Our proposed approach, MOGAT, outperforms MOGONET by 32% to 46% and SUPREME by 2% to 16% in cancer subtype prediction in different scenarios, supporting our hypothesis. Our results also showed that GAT embeddings provide a better prognosis in differentiating the high-risk group from the low-risk group than raw features.


Assuntos
Pesquisa Biomédica , Neoplasias da Mama , Humanos , Feminino , Multiômica , Gerenciamento Clínico , Aprendizado de Máquina
19.
World J Microbiol Biotechnol ; 40(6): 193, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709343

RESUMO

The rapid industrial revolution significantly increased heavy metal pollution, becoming a major global environmental concern. This pollution is considered as one of the most harmful and toxic threats to all environmental components (air, soil, water, animals, and plants until reaching to human). Therefore, scientists try to find a promising and eco-friendly technique to solve this problem i.e., bacterial bioremediation. Various heavy metal resistance mechanisms were reported. Omics technologies can significantly improve our understanding of heavy metal resistant bacteria and their communities. They are a potent tool for investigating the adaptation processes of microbes in severe conditions. These omics methods provide unique benefits for investigating metabolic alterations, microbial diversity, and mechanisms of resistance of individual strains or communities to harsh conditions. Starting with genome sequencing which provides us with complete and comprehensive insight into the resistance mechanism of heavy metal resistant bacteria. Moreover, genome sequencing facilitates the opportunities to identify specific metal resistance genes, operons, and regulatory elements in the genomes of individual bacteria, understand the genetic mechanisms and variations responsible for heavy metal resistance within and between bacterial species in addition to the transcriptome, proteome that obtain the real expressed genes. Moreover, at the community level, metagenome, meta transcriptome and meta proteome participate in understanding the microbial interactive network potentially novel metabolic pathways, enzymes and gene species can all be found using these methods. This review presents the state of the art and anticipated developments in the use of omics technologies in the investigation of microbes used for heavy metal bioremediation.


Assuntos
Bactérias , Biodegradação Ambiental , Metais Pesados , Metais Pesados/metabolismo , Bactérias/genética , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Genoma Bacteriano , Proteômica , Transcriptoma , Metagenômica , Metagenoma , Genômica , Farmacorresistência Bacteriana/genética
20.
Trop Anim Health Prod ; 56(5): 182, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38825622

RESUMO

Proteomics, the large-scale study of proteins in biological systems has emerged as a pivotal tool in the field of animal and veterinary sciences, mainly for investigating local and rustic breeds. Proteomics provides valuable insights into biological processes underlying animal growth, reproduction, health, and disease. In this review, we highlight the key proteomics technologies, methodologies, and their applications in domestic animals, particularly in the tropical context. We also discuss advances in proteomics research, including integration of multi-omics data, single-cell proteomics, and proteogenomics, all of which are promising for improving animal health, adaptation, welfare, and productivity. However, proteomics research in domestic animals faces challenges, such as sample preparation variation, data quality control, privacy and ethical considerations relating to animal welfare. We also provide recommendations for overcoming these challenges, emphasizing the importance of following best practices in sample preparation, data quality control, and ethical compliance. We therefore aim for this review to harness the full potential of proteomics in advancing our understanding of animal biology and ultimately improve animal health and productivity in local breeds of diverse animal species in a tropical context.


Assuntos
Proteômica , Animais , Criação de Animais Domésticos/métodos , Clima Tropical , Animais Domésticos
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