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  1. Article ; Online: scConsensus: combining supervised and unsupervised clustering for cell type identification in single-cell RNA sequencing data.

    Ranjan, Bobby / Schmidt, Florian / Sun, Wenjie / Park, Jinyu / Honardoost, Mohammad Amin / Tan, Joanna / Arul Rayan, Nirmala / Prabhakar, Shyam

    BMC bioinformatics

    2021  Volume 22, Issue 1, Page(s) 186

    Abstract: Background: Clustering is a crucial step in the analysis of single-cell data. Clusters identified in an unsupervised manner are typically annotated to cell types based on differentially expressed genes. In contrast, supervised methods use a reference ... ...

    Abstract Background: Clustering is a crucial step in the analysis of single-cell data. Clusters identified in an unsupervised manner are typically annotated to cell types based on differentially expressed genes. In contrast, supervised methods use a reference panel of labelled transcriptomes to guide both clustering and cell type identification. Supervised and unsupervised clustering approaches have their distinct advantages and limitations. Therefore, they can lead to different but often complementary clustering results. Hence, a consensus approach leveraging the merits of both clustering paradigms could result in a more accurate clustering and a more precise cell type annotation.
    Results: We present SCCONSENSUS, an [Formula: see text] framework for generating a consensus clustering by (1) integrating results from both unsupervised and supervised approaches and (2) refining the consensus clusters using differentially expressed genes. The value of our approach is demonstrated on several existing single-cell RNA sequencing datasets, including data from sorted PBMC sub-populations.
    Conclusions: SCCONSENSUS combines the merits of unsupervised and supervised approaches to partition cells with better cluster separation and homogeneity, thereby increasing our confidence in detecting distinct cell types. SCCONSENSUS is implemented in [Formula: see text] and is freely available on GitHub at https://github.com/prabhakarlab/scConsensus .
    MeSH term(s) Cluster Analysis ; Gene Expression Profiling ; Leukocytes, Mononuclear ; RNA ; Sequence Analysis, RNA ; Single-Cell Analysis
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2021-04-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041484-5
    ISSN 1471-2105 ; 1471-2105
    ISSN (online) 1471-2105
    ISSN 1471-2105
    DOI 10.1186/s12859-021-04028-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes.

    Honardoost, Mohammad Amin / Adinatha, Andreas / Schmidt, Florian / Ranjan, Bobby / Ghaeidamini, Maryam / Arul Rayan, Nirmala / Gek Liang Lim, Michelle / Joanito, Ignasius / Xiao Xuan Lin, Quy / Rajagopalan, Deepa / Qi Mok, Shi / Hwang, You Yi / Larbi, Anis / Khor, Chiea Chuen / Foo, Roger / Boehm, Bernhard Otto / Prabhakar, Shyam

    Genome medicine

    2024  Volume 16, Issue 1, Page(s) 45

    Abstract: Background: Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting : Methods: In this cross-sectional analysis, we generated a single-cell ... ...

    Abstract Background: Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting
    Methods: In this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (stage 3) cases and 31 matched controls.
    Results: We surprisingly detected profound alterations in circulatory immune cells (1784 dysregulated genes in 13 immune cell types), far exceeding the count in the comparator systemic autoimmune disease SLE. Genes upregulated in T1DM were involved in WNT signaling, interferon signaling and migration of T/NK cells, antigen presentation by B cells, and monocyte activation. A significant fraction of these differentially expressed genes were also altered in T1DM pancreatic islets. We used the single-cell data to construct a T1DM metagene z-score (TMZ score) that distinguished cases and controls and classified patients into molecular subtypes. This score correlated with known prognostic immune markers of T1DM, as well as with drug response in clinical trials.
    Conclusions: Our study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes, and has the potential to guide non-invasive test development and patient stratification.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 1/genetics ; Leukocytes, Mononuclear/metabolism ; Cross-Sectional Studies ; Single-Cell Gene Expression Analysis ; Autoimmune Diseases
    Language English
    Publishing date 2024-03-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2484394-5
    ISSN 1756-994X ; 1756-994X
    ISSN (online) 1756-994X
    ISSN 1756-994X
    DOI 10.1186/s13073-024-01300-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Pathogenic Epigenetic Consequences of Genetic Alterations in IDH-Wild-Type Diffuse Astrocytic Gliomas.

    Ohka, Fumiharu / Shinjo, Keiko / Deguchi, Shoichi / Matsui, Yusuke / Okuno, Yusuke / Katsushima, Keisuke / Suzuki, Miho / Kato, Akira / Ogiso, Noboru / Yamamichi, Akane / Aoki, Kosuke / Suzuki, Hiromichi / Sato, Shinya / Arul Rayan, Nirmala / Prabhakar, Shyam / Göke, Jonathan / Shimamura, Teppei / Maruyama, Reo / Takahashi, Satoru /
    Suzumura, Akio / Kimura, Hiroshi / Wakabayashi, Toshihiko / Zong, Hui / Natsume, Atsushi / Kondo, Yutaka

    Cancer research

    2019  Volume 79, Issue 19, Page(s) 4814–4827

    Abstract: Gliomas are classified by combining histopathologic and molecular features, including isocitrate dehydrogenase ( ...

    Abstract Gliomas are classified by combining histopathologic and molecular features, including isocitrate dehydrogenase (
    MeSH term(s) Animals ; Astrocytoma/genetics ; Astrocytoma/metabolism ; Astrocytoma/pathology ; Enhancer of Zeste Homolog 2 Protein/genetics ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Epigenesis, Genetic/genetics ; Humans ; Isocitrate Dehydrogenase/genetics ; Mice ; Mice, Transgenic
    Chemical Substances Isocitrate Dehydrogenase (EC 1.1.1.41) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43)
    Language English
    Publishing date 2019-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-19-1272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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