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      Analysis of Gut Microbiota Signature and Microbe-Disease Progression Associations in Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Concurrent Chemoradiotherapy

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          Abstract

          Purpose

          To evaluate the association of gut microbiome signature and disease progression in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) by fecal metagenome analysis.

          Methods

          Metagenome-wide association studies on baseline fecal samples from 18 LA-NSCLC patients before CCRT and 13 controls from healthy first-degree relatives were performed. Among the 18 LA-NSCLC patients, six patients were defined as the long progression-free survival (long-PFS) group (PFS≥11 months) while another 12 were in the short-PFS group (PFS<11 months). Alpha diversity, taxonomic composition, and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways were compared between groups.

          Results

          The Firmicutes/Bacteroidetes value of long-PFS group was higher than those of short-PFS (p=0.073) and healthy individual groups (p=0.009). Meanwhile, long-PFS group had significantly higher diversities in Fungi, Archaea, and Viruses than short-PFS group. The KEGG pathways overrepresented in short-PFS group included fructose and mannose metabolism (p=0.028), streptomycin biosynthesis (p=0.028), acarbose and validamycin biosynthesis (p=0.013), ribosome biogenesis in eukaryotes (p=0.035), biosynthesis of vancomycin group antibiotics (p=0.004), apoptosis-fly (p=0.044), and tetracycline biosynthesis (p=0.044), while those overrepresented in long-PFS group included fatty acid biosynthesis (p=0.035), fatty acid metabolism (p=0.008), vancomycin resistance (p=0.008), longevity regulating pathway-worm (p=0.028), type II diabetes mellitus (p=0.004), and viral carcinogenesis (p=0.003). Further analysis of antibiotic resistome demonstrated that the short-PFS group had a trend with more antibiotic resistance genes than healthy control (p=0.070) and long-PFS groups (p=0.218). The vancomycin resistance sequences were significantly enriched in the long-PFS group compared to the short-PFS group (p=0.006).

          Conclusions

          The baseline gut microbiome composition and functionality might be associated with PFS in LA-NSCLC treated with CCRT. The outcome of CCRT might be modulated through bacterial metabolic pathways. The antibiotic resistance genes might play a role in disease progression and provide potential information on the relationship between the use of antibiotics and treatment efficacy of CCRT in LA-NSCLC.

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          Most cited references53

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          fastp: an ultra-fast all-in-one FASTQ preprocessor

          Abstract Motivation Quality control and preprocessing of FASTQ files are essential to providing clean data for downstream analysis. Traditionally, a different tool is used for each operation, such as quality control, adapter trimming and quality filtering. These tools are often insufficiently fast as most are developed using high-level programming languages (e.g. Python and Java) and provide limited multi-threading support. Reading and loading data multiple times also renders preprocessing slow and I/O inefficient. Results We developed fastp as an ultra-fast FASTQ preprocessor with useful quality control and data-filtering features. It can perform quality control, adapter trimming, quality filtering, per-read quality pruning and many other operations with a single scan of the FASTQ data. This tool is developed in C++ and has multi-threading support. Based on our evaluation, fastp is 2–5 times faster than other FASTQ preprocessing tools such as Trimmomatic or Cutadapt despite performing far more operations than similar tools. Availability and implementation The open-source code and corresponding instructions are available at https://github.com/OpenGene/fastp.
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            Fast and sensitive protein alignment using DIAMOND.

            The alignment of sequencing reads against a protein reference database is a major computational bottleneck in metagenomics and data-intensive evolutionary projects. Although recent tools offer improved performance over the gold standard BLASTX, they exhibit only a modest speedup or low sensitivity. We introduce DIAMOND, an open-source algorithm based on double indexing that is 20,000 times faster than BLASTX on short reads and has a similar degree of sensitivity.
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              CD-HIT: accelerated for clustering the next-generation sequencing data

              Summary: CD-HIT is a widely used program for clustering biological sequences to reduce sequence redundancy and improve the performance of other sequence analyses. In response to the rapid increase in the amount of sequencing data produced by the next-generation sequencing technologies, we have developed a new CD-HIT program accelerated with a novel parallelization strategy and some other techniques to allow efficient clustering of such datasets. Our tests demonstrated very good speedup derived from the parallelization for up to ∼24 cores and a quasi-linear speedup for up to ∼8 cores. The enhanced CD-HIT is capable of handling very large datasets in much shorter time than previous versions. Availability: http://cd-hit.org. Contact: liwz@sdsc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                01 June 2022
                2022
                : 12
                : 892401
                Affiliations
                [1] 1 School of Biology and Biological Engineering, South China University of Technology , Guangzhou, China
                [2] 2 Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences , Guangzhou, China
                [3] 3 Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat−sen University Cancer Center , Guangzhou, China
                Author notes

                Edited by: Guoliang Zhang, Shenzhen Third People’s Hospital, China

                Reviewed by: Ho Chun Loong, Southern University of Science and Technology, China; Yi Cai, Shenzhen University, China

                *Correspondence: Hui Liu, liuhuisysucc@ 123456sina.com ; QingPing Wu, wuqp203@ 123456163.com

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Microbiome in Health and Disease, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2022.892401
                9200620
                85247ae5-1850-44c4-a17a-7d0fecc56c44
                Copyright © 2022 Xi, Liu, Qiu, Li, Xie, Guo, Wu, Liang, Wang, Wang, Chen, Xue, Ding, Zhang, Wu and Liu

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 March 2022
                : 04 April 2022
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 53, Pages: 11, Words: 4834
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Funded by: National Key Research and Development Program of China , doi 10.13039/501100012166;
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                non-small cell lung cancer,gut microbiota,chemoradiotherapy,disease progression,metagenomes,antibiotic resistance genes

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