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1.
Brief Bioinform ; 24(1)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36585784

RESUMO

Single-cell RNA sequencing (scRNA-seq) clustering and labelling methods are used to determine precise cellular composition of tissue samples. Automated labelling methods rely on either unsupervised, cluster-based approaches or supervised, cell-based approaches to identify cell types. The high complexity of cancer poses a unique challenge, as tumor microenvironments are often composed of diverse cell subpopulations with unique functional effects that may lead to disease progression, metastasis and treatment resistance. Here, we assess 17 cell-based and 9 cluster-based scRNA-seq labelling algorithms using 8 cancer datasets, providing a comprehensive large-scale assessment of such methods in a cancer-specific context. Using several performance metrics, we show that cell-based methods generally achieved higher performance and were faster compared to cluster-based methods. Cluster-based methods more successfully labelled non-malignant cell types, likely because of a lack of gene signatures for relevant malignant cell subpopulations. Larger cell numbers present in some cell types in training data positively impacted prediction scores for cell-based methods. Finally, we examined which methods performed favorably when trained and tested on separate patient cohorts in scenarios similar to clinical applications, and which were able to accurately label particularly small or under-represented cell populations in the given datasets. We conclude that scPred and SVM show the best overall performances with cancer-specific data and provide further suggestions for algorithm selection. Our analysis pipeline for assessing the performance of cell type labelling algorithms is available in https://github.com/shooshtarilab/scRNAseq-Automated-Cell-Type-Labelling.


Assuntos
Neoplasias , Análise da Expressão Gênica de Célula Única , Humanos , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Algoritmos , Neoplasias/genética , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Microambiente Tumoral
2.
FEMS Microbiol Rev ; 33(1): 66-97, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19054114

RESUMO

The bacterial cell-envelope consists of a complex arrangement of lipids, proteins and carbohydrates that serves as the interface between a microorganism and its environment or, with pathogens, a human host. Escherichia coli has long been investigated as a leading model system to elucidate the fundamental mechanisms underlying microbial cell-envelope biology. This includes extensive descriptions of the molecular identities, biochemical activities and evolutionary trajectories of integral transmembrane proteins, many of which play critical roles in infectious disease and antibiotic resistance. Strikingly, however, only half of the c. 1200 putative cell-envelope-related proteins of E. coli currently have experimentally attributed functions, indicating an opportunity for discovery. In this review, we summarize the state of the art of computational and proteomic approaches for determining the components of the E. coli cell-envelope proteome, as well as exploring the physical and functional interactions that underlie its biogenesis and functionality. We also provide a comprehensive comparative benchmarking analysis on the performance of different bioinformatic and proteomic methods commonly used to determine the subcellular localization of bacterial proteins.


Assuntos
Proteínas da Membrana Bacteriana Externa/análise , Biologia Computacional/métodos , Proteínas de Escherichia coli/química , Escherichia coli/química , Proteoma/química , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Ligação Proteica , Mapeamento de Interação de Proteínas , Transporte Proteico , Proteoma/genética , Proteoma/metabolismo
3.
Genome Biol ; 8(2): R26, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17326820

RESUMO

BACKGROUND: Gene duplication followed by divergence is one of the main sources of metabolic versatility. The patchwork and stepwise models of metabolic evolution help us to understand these processes, but their assumptions are relatively simplistic. We used a network-based approach to determine the influence of metabolic constraints on the retention of duplicated genes. RESULTS: We detected duplicated genes by looking for enzymes sharing homologous domains and uncovered an increased retention of duplicates for enzymes catalyzing consecutive reactions, as illustrated by the ligases acting in the biosynthesis of peptidoglycan. As a consequence, metabolic networks show a high retention of duplicates within functional modules, and we found a preferential biochemical coupling of reactions that partially explains this bias. A similar situation was found in enzyme-enzyme interaction networks, but not in interaction networks of non-enzymatic proteins or gene transcriptional regulatory networks, suggesting that the retention of duplicates results from the biochemical rules governing substrate-enzyme-product relationships. We confirmed a high retention of duplicates between chemically similar reactions, as illustrated by fatty-acid metabolism. The retention of duplicates between chemically dissimilar reactions is, however, also greater than expected by chance. Finally, we detected a significant retention of duplicates as groups, instead of single pairs. CONCLUSION: Our results indicate that in silico modeling of the origin and evolution of metabolism is improved by the inclusion of specific functional constraints, such as the preferential biochemical coupling of reactions. We suggest that the stepwise and patchwork models are not independent of each other: in fact, the network perspective enables us to reconcile and combine these models.


Assuntos
Enzimas/genética , Evolução Molecular , Duplicação Gênica , Metabolismo/genética , Modelos Genéticos , Sequência de Aminoácidos , Biologia Computacional , Bases de Dados Genéticas , Genes Duplicados/genética , Dados de Sequência Molecular
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