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  1. Article ; Online: Supervised capacity preserving mapping: a clustering guided visualization method for scRNA-seq data.

    Zhai, Zhiqian / Lei, Yu L / Wang, Rongrong / Xie, Yuying

    Bioinformatics (Oxford, England)

    2022  Volume 38, Issue 9, Page(s) 2496–2503

    Abstract: Motivation: The rapid development of scRNA-seq technologies enables us to explore the transcriptome at the cell level on a large scale. Recently, various computational methods have been developed to analyze the scRNAseq data, such as clustering and ... ...

    Abstract Motivation: The rapid development of scRNA-seq technologies enables us to explore the transcriptome at the cell level on a large scale. Recently, various computational methods have been developed to analyze the scRNAseq data, such as clustering and visualization. However, current visualization methods, including t-SNE and UMAP, are challenged by the limited accuracy of rendering the geometric relationship of populations with distinct functional states. Most visualization methods are unsupervised, leaving out information from the clustering results or given labels. This leads to the inaccurate depiction of the distances between the bona fide functional states. In particular, UMAP and t-SNE are not optimal to preserve the global geometric structure. They may result in a contradiction that clusters with near distance in the embedded dimensions are in fact further away in the original dimensions. Besides, UMAP and t-SNE cannot track the variance of clusters. Through the embedding of t-SNE and UMAP, the variance of a cluster is not only associated with the true variance but also is proportional to the sample size.
    Results: We present supCPM, a robust supervised visualization method, which separates different clusters, preserves the global structure and tracks the cluster variance. Compared with six visualization methods using synthetic and real datasets, supCPM shows improved performance than other methods in preserving the global geometric structure and data variance. Overall, supCPM provides an enhanced visualization pipeline to assist the interpretation of functional transition and accurately depict population segregation.
    Availability and implementation: The R package and source code are available at https://zenodo.org/record/5975977#.YgqR1PXMJjM.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Single-Cell Analysis/methods ; Sequence Analysis, RNA/methods ; Gene Expression Profiling/methods ; Algorithms ; Cluster Analysis
    Language English
    Publishing date 2022-02-24
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btac131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Generation and Culture of Mouse Embryonic Fibroblasts.

    Tan, Yee Sun / Lei, Yu L

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 1960, Page(s) 85–91

    Abstract: In addition to leukocytes, a variety of cells also participate in the innate immune response, including endothelial cells, epithelial cells, and fibroblasts. Thus, the study of these cells is highly relevant in broadening our understanding of mechanisms ... ...

    Abstract In addition to leukocytes, a variety of cells also participate in the innate immune response, including endothelial cells, epithelial cells, and fibroblasts. Thus, the study of these cells is highly relevant in broadening our understanding of mechanisms that modulate innate immunity. With the rise of genetically engineered animals, it is now common to confirm in vitro data acquired using immortalized cell lines with more physiologically relevant primary cells from these animals ex vivo. Indeed, many studies exploring innate immune system function employ mouse embryonic fibroblasts (MEFs). These cells are relatively simple to generate and are a powerful tool to explore regulatory networks, examine biochemical profiling of protein complexes, and investigate novel signaling pathways associated with innate immune system signaling. Here, we provide a robust protocol to isolate, maintain, and store primary MEFs. This protocol is designed for users with minimal experience using mouse models. We have also added precautions and common pitfalls associated with these procedures.
    MeSH term(s) Animals ; Cell Culture Techniques ; Cell Differentiation/physiology ; Embryo, Mammalian/cytology ; Embryo, Mammalian/metabolism ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Fibroblasts/cytology ; Mice ; Signal Transduction/physiology
    Language English
    Publishing date 2019-02-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9167-9_7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Isolation of Tumor-Infiltrating Lymphocytes by Ficoll-Paque Density Gradient Centrifugation.

    Tan, Yee Sun / Lei, Yu L

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 1960, Page(s) 93–99

    Abstract: With the renewed enthusiasm in immuno-oncology, characterization of the tumor immune microenvironment constitutes an essential and unique aspect to the assessment of therapeutics. The isolation of tumor-infiltrating lymphocytes (TILs) is a desirable ... ...

    Abstract With the renewed enthusiasm in immuno-oncology, characterization of the tumor immune microenvironment constitutes an essential and unique aspect to the assessment of therapeutics. The isolation of tumor-infiltrating lymphocytes (TILs) is a desirable approach toward the understanding of antitumor immune response. This chapter provides an effective protocol to mechanically dissociate tumor tissue and generate single-cell suspension from excised tumors. TILs are then isolated by Ficoll-Paque density gradient centrifugation. This protocol is applicable to both human and experimental tumors in immunocompetent murine models.
    MeSH term(s) Animals ; Cell Separation/methods ; Centrifugation, Density Gradient/methods ; Humans ; Lymphocytes, Tumor-Infiltrating/cytology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Tumor Microenvironment/genetics ; Tumor Microenvironment/physiology
    Language English
    Publishing date 2019-02-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9167-9_8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Immune deserts in head and neck squamous cell carcinoma: A review of challenges and opportunities for modulating the tumor immune microenvironment.

    Farlow, Janice L / Brenner, J Chad / Lei, Yu L / Chinn, Steven B

    Oral oncology

    2021  Volume 120, Page(s) 105420

    Abstract: Immunotherapy revolutionized cancer treatment but has yet to elicit durable responses in the majority of patients with head and neck squamous cell carcinoma (HNSCC). HNSCC is generally characterized by a high tumor mutational burden, which has translated ...

    Abstract Immunotherapy revolutionized cancer treatment but has yet to elicit durable responses in the majority of patients with head and neck squamous cell carcinoma (HNSCC). HNSCC is generally characterized by a high tumor mutational burden, which has translated to a large neoantigen load that could prime the immune system to recognize and eliminate malignant cells. Studies are increasingly showing, however, that HNSCC is an "immune desert" tumor that can hijack multiple parts of the tumor immunity cycle in order to evade immune recognition and suppress immune system activation. Herein we will review how HNSCC tumors modulate their architecture, cellular composition, and cytokine milieu to maximize immunosuppression; as well as relevant therapeutic opportunities and emerging issues facing the field of HNSCC immuno-oncology.
    MeSH term(s) Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/therapy ; Humans ; Immune System ; Immunotherapy ; Squamous Cell Carcinoma of Head and Neck/immunology ; Squamous Cell Carcinoma of Head and Neck/therapy ; Tumor Microenvironment
    Language English
    Publishing date 2021-07-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 0964-1955 ; 1368-8375
    ISSN (online) 1879-0593
    ISSN 0964-1955 ; 1368-8375
    DOI 10.1016/j.oraloncology.2021.105420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The Interactions Between

    Zhou, Yujie / Cheng, Lei / Lei, Yu L / Ren, Biao / Zhou, Xuedong

    Frontiers in microbiology

    2021  Volume 12, Page(s) 652725

    Abstract: Mucosa protects the body against external pathogen invasion. However, pathogen colonies on the mucosa can invade the mucosa when the immunosurveillance is compromised, causing mucosal infection and subsequent diseases. Therefore, it is necessary to ... ...

    Abstract Mucosa protects the body against external pathogen invasion. However, pathogen colonies on the mucosa can invade the mucosa when the immunosurveillance is compromised, causing mucosal infection and subsequent diseases. Therefore, it is necessary to timely and effectively monitor and control pathogenic microorganisms through mucosal immunity.
    Language English
    Publishing date 2021-06-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.652725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Inhibition of

    Chen, Jianwen / Zhao, Bao / Li, Tianliang / Dong, Hong / Cheng, Xiang / Gong, Wang / Wang, Jing / Zhang, Junran / Xin, Gang / Yu, Yanbao / Lei, Yu L / Black, Jennifer D / Li, Zihai / Wen, Haitao

    bioRxiv : the preprint server for biology

    2023  

    Abstract: ... ...

    Abstract The
    Language English
    Publishing date 2023-12-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.14.571787
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Fast and robust deconvolution of tumor infiltrating lymphocyte from expression profiles using least trimmed squares.

    Hao, Yuning / Yan, Ming / Heath, Blake R / Lei, Yu L / Xie, Yuying

    PLoS computational biology

    2019  Volume 15, Issue 5, Page(s) e1006976

    Abstract: Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major ... ...

    Abstract Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative to develop a robust deconvolution method that automatically decontaminates data by reliably detecting and removing outliers. We developed a new machine learning tool, Fast And Robust DEconvolution of Expression Profiles (FARDEEP), to enumerate immune cell subsets from whole tumor tissue samples. To reduce noise in the tumor gene expression datasets, FARDEEP utilizes an adaptive least trimmed square to automatically detect and remove outliers before estimating the cell compositions. We show that FARDEEP is less susceptible to outliers and returns a better estimation of coefficients than the existing methods with both numerical simulations and real datasets. FARDEEP provides an estimate related to the absolute quantity of each immune cell subset in addition to relative percentages. Hence, FARDEEP represents a novel robust algorithm to complement the existing toolkit for the characterization of tissue-infiltrating immune cell landscape. The source code for FARDEEP is implemented in R and available for download at https://github.com/YuningHao/FARDEEP.git.
    MeSH term(s) Algorithms ; Gene Expression Profiling/methods ; Gene Expression Regulation/genetics ; Humans ; Least-Squares Analysis ; Lymphocytes, Tumor-Infiltrating/metabolism ; Neoplasms/genetics ; Sequence Analysis, DNA/methods ; Software ; Transcriptome/genetics
    Language English
    Publishing date 2019-05-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1006976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments.

    Raghavan, Shreya / Mehta, Pooja / Xie, Yuying / Lei, Yu L / Mehta, Geeta

    Journal for immunotherapy of cancer

    2019  Volume 7, Issue 1, Page(s) 190

    Abstract: Background: Innate immune cells such as macrophages are abundantly present within malignant ascites, where they share the microenvironment with ovarian cancer stem cells (CSC).: Methods: To mimic this malignant ascites microenvironment, we created a ... ...

    Abstract Background: Innate immune cells such as macrophages are abundantly present within malignant ascites, where they share the microenvironment with ovarian cancer stem cells (CSC).
    Methods: To mimic this malignant ascites microenvironment, we created a hanging-drop hetero-spheroid model to bring CSCs and macrophages in close association. Within these hetero-spheroids, CD68
    Results: Our results indicate that CSCs drive the upregulation of M2 macrophage marker CD206 within hetero-spheroids, compared to bulk ovarian cancer cells, implying an inherently more immuno-suppressive program. Moreover, an increased maintenance of elevated aldehyde dehydrogenase (ALDH) activity is noted within hetero-spheroids that include pre-polarized CD206
    Conclusions: Our data implies that macrophage- initiated WNT signaling could play a significant role in the maintenance of stemness, and the resulting phenotypes of chemoresistance and invasiveness. Our results indicate paracrine WNT activation during CSC/M2 macrophages interaction constitutes a positive feedback loop that likely contributes to the more aggressive phenotype, which makes the WNT pathway a potential target to reduce the CSC and M2 macrophage compartments in the tumor microenvironment.
    MeSH term(s) Animals ; Cell Line, Tumor ; Coculture Techniques ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Macrophages/immunology ; Macrophages/pathology ; Mice ; Neoplasm Transplantation ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/pathology ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/pathology ; Phenotype ; Spheroids, Cellular/immunology ; Spheroids, Cellular/pathology ; Tumor Microenvironment ; Wnt Signaling Pathway
    Language English
    Publishing date 2019-07-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1186/s40425-019-0666-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Repression of ferroptotic cell death by mitochondrial calcium signaling.

    Chen, Jianwen / Zhao, Bao / Wang, Shen / Ma, Anjun / Dong, Hong / Cheng, Xiang / Lin, Shengyin / Li, Xinghui / Herring, Laura E / Xin, Gang / Ma, Qin / He, Kai / Xie, Ruili / Lei, Yu L / Ingold, Irina / Cheng, Xiaolin / Li, Zihai / Wen, Haitao

    Research square

    2023  

    Abstract: The uptake of ... ...

    Abstract The uptake of Ca
    Language English
    Publishing date 2023-07-10
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-3029860/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Combined Pik3ca-H1047R and loss-of-function Notch1 alleles decrease survival time in a 4-nitroquinoline N-oxide-driven head and neck squamous cell carcinoma model.

    Michmerhuizen, Nicole L / Heenan, Caitlin / Wang, Jiayu / Leonard, Elizabeth / Bellile, Emily / Loganathan, Sampath K / Wong, Sunny Y / Lei, Yu L / Brenner, J Chad

    Oral oncology

    2022  Volume 126, Page(s) 105770

    MeSH term(s) 4-Nitroquinoline-1-oxide ; Alleles ; Class I Phosphatidylinositol 3-Kinases/genetics ; Head and Neck Neoplasms/genetics ; Humans ; Mutation ; Oxides ; Receptor, Notch1/genetics ; Squamous Cell Carcinoma of Head and Neck
    Chemical Substances NOTCH1 protein, human ; Oxides ; Receptor, Notch1 ; 4-Nitroquinoline-1-oxide (56-57-5) ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137)
    Language English
    Publishing date 2022-02-13
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 1120465-5
    ISSN 1879-0593 ; 0964-1955 ; 1368-8375
    ISSN (online) 1879-0593
    ISSN 0964-1955 ; 1368-8375
    DOI 10.1016/j.oraloncology.2022.105770
    Database MEDical Literature Analysis and Retrieval System OnLINE

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