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      Machine learning-assisted immune profiling stratifies peri-implantitis patients with unique microbial colonization and clinical outcomes

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          Abstract

          Rationale: The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system.

          Methods: We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and microbial profiling. We utilized a robust outlier-resistant machine learning algorithm for immune deconvolution.

          Results: Unsupervised clustering identified risk groups with distinct immune profiles, microbial colonization dynamics, and regenerative outcomes. Low-risk patients exhibited elevated M1/M2-like macrophage ratios and lower B-cell infiltration. The low-risk immune profile was characterized by enhanced complement signaling and higher levels of Th1 and Th17 cytokines. Fusobacterium nucleatum and Prevotella intermedia were significantly enriched in high-risk individuals. Although surgery reduced microbial burden at the peri-implant interface in all groups, only low-risk individuals exhibited suppression of keystone pathogen re-colonization.

          Conclusion: Peri-implant immune microenvironment shapes microbial composition and the course of regeneration. Immune signatures show untapped potential in improving the risk-grading for peri-implantitis.

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          Most cited references36

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          DADA2: High resolution sample inference from Illumina amplicon data

          We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
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            Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2

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              Robust enumeration of cell subsets from tissue expression profiles

              We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA mixtures for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).
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                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2021
                3 May 2021
                : 11
                : 14
                : 6703-6716
                Affiliations
                [1 ]Department of Periodontics and Oral Medicine, the University of Michigan School of Dentistry, Ann Arbor, MI 48109.
                [2 ]Department of Computational Mathematics, Science, and Engineering, Michigan State University, East Lansing, MI 48823.
                [3 ]Department of Biomedical Engineering, College of Engineering & Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109.
                [4 ]Division of Gastroenterology and Hepatology, Department of Internal Medicine, the University of Michigan Medical School, Ann Arbor, MI 48105.
                [5 ]Rogel Cancer Center, the University of Michigan, Ann Arbor, MI 48105.
                [6 ]Current Affiliation: Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA 02115.
                Author notes
                ✉ Corresponding authors: Yu Leo Lei, DDS, PhD, 1600 Huron Parkway 2355, Ann Arbor, MI 48109. Phone: 734-615-6967; FAX: 734-763-5503; E-mail: leiyuleo@ 123456umich.edu ; William V. Giannobile, DDS, DMSc, 188 Longwood Avenue, Boston, MA 02115. Phone: 617-432-1401; FAX: 617-432-4266; E-mail: william_giannobile@ 123456hsdm.harvard.edu ; Yuying Xie, PhD, PhD, 428 South Shaw Ln, 1513 Engineering Building. Phone: 517-432-0391; E-mail: xyy@ 123456msu.edu .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov11p6703
                10.7150/thno.57775
                8171076
                34093848
                df7a9b04-b5eb-46b0-8511-dfb9365a3e9b
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 3 January 2021
                : 31 March 2021
                Categories
                Research Paper

                Molecular medicine
                peri-implantitis,classification,immune profiling,microbiome,fardeep
                Molecular medicine
                peri-implantitis, classification, immune profiling, microbiome, fardeep

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