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Successive High-Resolution (H₂O)_n-GCIB and C₆₀-SIMS Imaging Integrates Multi-Omics in Different Cell Types in Breast Cancer Tissue.

ABSTRACT: The temporo-spatial organization of different cells in the tumor microenvironment (TME) is the key to understanding their complex communication networks and the immune landscape that exists within compromised tissues. Multi-omics profiling of single-interacting cells in the native TME is critical for providing further information regarding the reprograming mechanisms leading to immunosuppression and tumor progression. This requires new technologies for biomolecular profiling of phenotypically heterogeneous cells on the same tissue sample. Here, we developed a new methodology for comprehensive lipidomic and metabolomic profiling of individual cells on frozen-hydrated tissue sections using water gas cluster ion beam secondary ion mass spectrometry ((H₂O)_n-GCIB-SIMS) (at 1.6 μm beam spot size), followed by profiling cell-type specific lanthanide antibodies on the same tissue section using C₆₀-SIMS (at 1.1 μm beam spot size). We revealed distinct variations of distribution and intensities of >150 key ions (e.g., lipids and important metabolites) in different types of the TME individual cells, such as actively proliferating tumor cells as well as infiltrating immune cells. The demonstrated feasibility of SIMS imaging to integrate the multi-omics profiling in the same tissue section at the single-cell level will lead to new insights into the role of lipid reprogramming and metabolic response in normal regulation or pathogenic discoordination of cell-cell interactions in a variety of tissue microenvironments.

SUBMITTER: Tian H

PROVIDER: S-EPMC8209780 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLncRNAs (Long non-coding RNAs) are a type of non-coding RNA molecule with transcript length longer than 200 nucleotides. LncRNA has been novel candidate biomarkers in cancer diagnosis and prognosis. However, it is difficult to discover the true association mechanism between lncRNAs and complex diseases. The unprecedented enrichment of multi-omics data and the rapid development of machine learning technology provide us with the opportunity to design a machine learning framework to study the relationship between lncRNAs and complex diseases.ResultsIn this article, we proposed a new machine learning approach, namely LGDLDA (LncRNA-Gene-Disease association networks based LncRNA-Disease Association prediction), for disease-related lncRNAs association prediction based multi-omics data, machine learning methods and neural network neighborhood information aggregation. Firstly, LGDLDA calculates the similarity matrix of lncRNA, gene and disease respectively, and it calculates the similarity between lncRNAs through the lncRNA expression profile matrix, lncRNA-miRNA interaction matrix and lncRNA-protein interaction matrix. We obtain gene similarity matrix by calculating the lncRNA-gene association matrix and the gene-disease association matrix, and we obtain disease similarity matrix by calculating the disease ontology, the disease-miRNA association matrix, and Gaussian interaction profile kernel similarity. Secondly, LGDLDA integrates the neighborhood information in similarity matrices by using nonlinear feature learning of neural network. Thirdly, LGDLDA uses embedded node representations to approximate the observed matrices. Finally, LGDLDA ranks candidate lncRNA-disease pairs and then selects potential disease-related lncRNAs.ConclusionsCompared with lncRNA-disease prediction methods, our proposed method takes into account more critical information and obtains the performance improvement cancer-related lncRNA predictions. Randomly split data experiment results show that the stability of LGDLDA is better than IDHI-MIRW, NCPLDA, LncDisAP and NCPHLDA. The results on different simulation data sets show that LGDLDA can accurately and effectively predict the disease-related lncRNAs. Furthermore, we applied the method to three real cancer data including gastric cancer, colorectal cancer and breast cancer to predict potential cancer-related lncRNAs.

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Successive High-Resolution (H₂O)_n-GCIB and C₆₀-SIMS Imaging Integrates Multi-Omics in Different Cell Types in Breast Cancer Tissue.

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OmicsDI is part of the ELIXIR infrastructure

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Successive High-Resolution (H2O)n-GCIB and C60-SIMS Imaging Integrates Multi-Omics in Different Cell Types in Breast Cancer Tissue.

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OmicsDI is part of the ELIXIR infrastructure

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Successive High-Resolution (H₂O)_n-GCIB and C₆₀-SIMS Imaging Integrates Multi-Omics in Different Cell Types in Breast Cancer Tissue.