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A review on computational models for predicting protein solubility
Teerapat Pimtawong, Jun Ren, Jingyu Lee, Hyang-Mi Lee, Dokyun Na
J. Microbiol. 2025;63(1):e.2408001.   Published online January 24, 2025
DOI: https://doi.org/10.71150/jm.2408001
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AbstractAbstract PDF

Protein solubility is a critical factor in the production of recombinant proteins, which are widely used in various industries, including pharmaceuticals, diagnostics, and biotechnology. Predicting protein solubility remains a challenging task due to the complexity of protein structures and the multitude of factors influencing solubility. Recent advances in computational methods, particularly those based on machine learning, have provided powerful tools for predicting protein solubility, thereby reducing the need for extensive experimental trials. This review provides an overview of current computational approaches to predict protein solubility. We discuss the datasets, features, and algorithms employed in these models. The review aims to bridge the gap between computational predictions and experimental validations, fostering the development of more accurate and reliable solubility prediction models that can significantly enhance recombinant protein production.

Journal Articles
Regulator of ribonuclease activity modulates the pathogenicity of Vibrio vulnificus
Jaejin Lee , Eunkyoung Shin , Jaeyeong Park , Minho Lee , Kangseok Lee
J. Microbiol. 2021;59(12):1133-1141.   Published online November 9, 2021
DOI: https://doi.org/10.1007/s12275-021-1518-5
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AbstractAbstract
RraA, a protein regulator of RNase E activity, plays a unique role in modulating the mRNA abundance in Escherichia coli. The marine pathogenic bacterium Vibrio vulnificus also possesses homologs of RNase E (VvRNase E) and RraA (VvRraA1 and VvRraA2). However, their physiological roles have not yet been investigated. In this study, we demonstrated that VvRraA1 expression levels affect the pathogenicity of V. vulnificus. Compared to the wild-type strain, the VvrraA1-deleted strain (ΔVvrraA1) showed decreased motility, invasiveness, biofilm formation ability as well as virulence in mice; these phenotypic changes of ΔVvrraA1 were restored by the exogenous expression of VvrraA1. Transcriptomic analysis indicated that VvRraA1 expression levels affect the abundance of a large number of mRNA species. Among them, the halflives of mRNA species encoding virulence factors (e.g., smcR and htpG) that have been previously shown to affect VvrraA1 expression-dependent phenotypes were positively correlated with VvrraA1 expression levels. These findings suggest that VvRraA1 modulates the pathogenicity of V. vulnificus by regulating the abundance of a subset of mRNA species.

Citations

Citations to this article as recorded by  
  • Identification of the global regulatory roles of RraA via the integrative transcriptome and proteome in Vibrio alginolyticus
    Huizhen Chen, Qian Gao, Bing Liu, Ying Zhang, Jianxiang Fang, Songbiao Wang, Youqi Chen, Chang Chen, Nicolas E. Buchler
    mSphere.2024;[Epub]     CrossRef
  • Comparative Transcriptomic Analysis of Flagellar-Associated Genes in Salmonella Typhimurium and Its rnc Mutant
    Seungmok Han, Ji-Won Byun, Minho Lee
    Journal of Microbiology.2024; 62(1): 33.     CrossRef
  • Eco-Evolutionary Drivers of Vibrio parahaemolyticus Sequence Type 3 Expansion: Retrospective Machine Learning Approach
    Amy Marie Campbell, Chris Hauton, Ronny van Aerle, Jaime Martinez-Urtaza
    JMIR Bioinformatics and Biotechnology.2024; 5: e62747.     CrossRef
  • Relaxed Cleavage Specificity of Hyperactive Variants of Escherichia coli RNase E on RNA I
    Dayeong Bae, Hana Hyeon, Eunkyoung Shin, Ji-Hyun Yeom, Kangseok Lee
    Journal of Microbiology.2023; 61(2): 211.     CrossRef
  • Regulator of RNase E activity modulates the pathogenicity of Salmonella Typhimurium
    Jaejin Lee, Eunkyoung Shin, Ji-Hyun Yeom, Jaeyoung Park, Sunwoo Kim, Minho Lee, Kangseok Lee
    Microbial Pathogenesis.2022; 165: 105460.     CrossRef
Ganoderma boninense mycelia for phytochemicals and secondary metabolites with antibacterial activity
Syahriel Abdullah , Se-Eun Jang , Min-Kyu Kwak , KhimPhin Chong
J. Microbiol. 2020;58(12):1054-1064.   Published online December 2, 2020
DOI: https://doi.org/10.1007/s12275-020-0208-z
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AbstractAbstract
Antiplasmodial nortriterpenes with 3,4-seco-27-norlanostane skeletons, almost entirely obtained from fruiting bodies, represent the main evidential source for bioactive secondary metabolites derived from a relatively unexplored phytopathogenic fungus, Ganoderma boninense. Currently lacking is convincing evidence for antimicrobial secondary metabolites in this pathogen, excluding that obtained from commonly observed phytochemicals in the plants. Herein, we aimed to demonstrate an efficient analytical approach for the production of antibacterial secondary metabolites using the mycelial extract of G. boninense. Three experimental cultures were prepared from fruiting bodies (GBFB), mycelium cultured on potato dextrose agar (PDA) media (GBMA), and liquid broth (GBMB). Through solvent extraction, culture type-dependent phytochemical distributions were diversely exhibited. Water-extracted GBMB produced the highest yield (31.21 ± 0.61%, p < 0.05), but both GBFB and GBMA elicited remarkably higher yields than GBMB when polar-organic solvent extraction was employed. Greater quantities of phytochemicals were also obtained from GBFB and GBMA, in sharp contrast to those gleaned from GBMB. However, the highest antibacterial activity was observed in chloroform-extracted GBMA against all tested bacteria. From liquid-liquid extractions (LLE), it was seen that mycelia extraction with combined chloroform-methanol-water at a ratio of 1:1:1 was superior at detecting antibacterial activities with the most significant quantities of antibacterial compounds. The data demonstrate a novel means of assessing antibacterial compounds with mycelia by LLE which avoids the shortcomings of standardized
method
ologies. Additionally, the antibacterial extract from the mycelia demonstrate that previously unknown bioactive secondary metabolites of the less studied subsets of Ganoderma may serve as active and potent antimicrobial compounds.

Citations

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  • Optimization of Ganoderma lingzhi triterpene extraction method and its hypoglycemic activity
    Shuang Hua, Yanshuang Li, Feng Jin, Meiyao Gan, Xianshun Jiang, Ying Zhang, Bo Zhang, Xiao Li
    Preparative Biochemistry & Biotechnology.2025; : 1.     CrossRef
  • Quorum Sensing and Mobility Inhibition of Pathogenic Bacteria by Fulvifomes mexicanus sp. nov.
    Angelica Bolaños-Nuñez, Michelle Martínez-Pineda, Ricardo Valenzuela, Mario Figueroa, Albert D. Patiño, Everardo Curiel-Quesada, César Ramiro Martínez-Gonzáles, Rodrigo Villanueva-Silva, Tania Raymundo, Abigail Pérez-Valdespino
    Molecules.2025; 30(11): 2278.     CrossRef
  • Exploring the health benefits of Ganoderma: antimicrobial properties and mechanisms of action
    Samantha C. Karunarathna, Nimesha M. Patabendige, Kalani K. Hapuarachchi, Itthayakorn Promputtha
    Frontiers in Cellular and Infection Microbiology.2025;[Epub]     CrossRef
  • Medium composition optimization and characterization of polysaccharides extracted from Ganoderma boninense along with antioxidant activity
    Qian-Zhu Li, Chuan Xiong, Wei Chee Wong, Li-Wei Zhou
    International Journal of Biological Macromolecules.2024; 260: 129528.     CrossRef
  • Cytotoxic Potential of Diospyros villosa Leaves and Stem Bark Extracts and Their Silver Nanoparticles
    Oluwatosin Temilade Adu, Yougasphree Naidoo, Johnson Lin, Depika Dwarka, John Mellem, Hosakatte Niranjana Murthy, Yaser Hassan Dewir
    Plants.2023; 12(4): 769.     CrossRef
  • The antitumor effect of mycelia extract of the medicinal macrofungus Inonotus hispidus on HeLa cells via the mitochondrial-mediated pathway
    Shao-Jun Tang, Chen-Xia Shao, Yi Yang, Rui Ren, Lei Jin, Dan Hu, Shen-Lian Wu, Pin Lei, Yue-Lin He, Jun Xu
    Journal of Ethnopharmacology.2023; 311: 116407.     CrossRef
  • Impacts of Plant-derived Secondary Metabolites for Improving Flora in Type 2 Diabetes
    Lin Zehao Li, Yan Yan, Qinghe Song, Zhibin Wang, Wei Zhang, Yanli Hou, Xiandang Zhang
    Current Diabetes Reviews.2023;[Epub]     CrossRef
  • Bioactive Compounds of Ganoderma boninense Inhibited Methicillin-Resistant Staphylococcus aureus Growth by Affecting Their Cell Membrane Permeability and Integrity
    Yow-San Chan, Khim-Phin Chong
    Molecules.2022; 27(3): 838.     CrossRef
  • Natural Products Targeting Liver X Receptors or Farnesoid X Receptor
    Jianglian She, Tanwei Gu, Xiaoyan Pang, Yonghong Liu, Lan Tang, Xuefeng Zhou
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • Biophysical characterization of antibacterial compounds derived from pathogenic fungi Ganoderma boninense
    Syahriel Abdullah, Yoon Sin Oh, Min-Kyu Kwak, KhimPhin Chong
    Journal of Microbiology.2021; 59(2): 164.     CrossRef
  • Enhanced Accumulation of Betulinic Acid in Transgenic Hairy Roots of Senna obtusifolia Growing in the Sprinkle Bioreactor and Evaluation of Their Biological Properties in Various Biological Models
    Tomasz Kowalczyk, Przemysław Sitarek, Monika Toma, Patricia Rijo, Eva Domínguez‐Martín, Irene Falcó, Gloria Sánchez, Tomasz Śliwiński
    Chemistry & Biodiversity.2021;[Epub]     CrossRef
Chitosan-chelated zinc modulates cecal microbiota and attenuates inflammatory response in weaned rats challenged with Escherichia coli
Dan Feng , Minyang Zhang , Shiyi Tian , Jing Wang , Weiyun Zhu
J. Microbiol. 2020;58(9):780-792.   Published online September 1, 2020
DOI: https://doi.org/10.1007/s12275-020-0056-x
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AbstractAbstract
Escherichia coli (E. coli) infection is very common among young growing animals, and zinc supplementation is often used to alleviate inflammation induced by this disease. Therefore, the objective of this study was to evaluate whether chitosan- chelated zinc (CS-Zn) supplementation could attenuate gut injury induced by E. coli challenge and to explore how CSZn modulates cecal microbiota and alleviates intestinal inflammation in weaned rats challenged with E. coli. 36 weaned rats (55.65 ± 2.18 g of BW, n = 12) were divided into three treatment groups consisting of unchallenged rats fed a basal diet (Control) and two groups of rats challenged with E. coli and fed a basal diet or a diet containing 640 mg/kg CS-Zn (E. coli + CS-Zn, containing 50 mg/kg Zn) for a 14-day experiment. On days 10 to 12, each rat was given 4 ml of E. coli solution with a total bacteria count of 1010 CFU by oral gavage daily or normal saline of equal dosage. CS-Zn supplementation mitigated intestinal morphology impairment (e.g. higher crypt depth and lower macroscopic damage index) induced by E. coli challenge (P < 0.05), and alleviated the increase of Myeloperoxidase (MPO) activity after E. coli challenge (P < 0.05). 16S rRNA sequencing analyses revealed that E. coli challenge significantly increased the abundance of Verrucomicrobia and E. coli (P < 0.05). However, CS-Zn supplementation increased the abundance of Lactobacillus and decreased the relative abundance of Proteobacteria, Desulfovibrio and E. coli (P < 0.05). The concentrations of butyrate in the cecal digesta, which decreased due to the challenge, were higher in the E. coli + CS-Zn group (P < 0.05). In addition, CS-Zn supplementation significantly prevented the elevation of pro-inflammatory cytokines IL-6 concentration and upregulated the level of anti-inflammatory cytokines IL-10 in cecal mucosa induced by E. coli infection (P < 0.05). In conclusion, these results indicate that CS-Zn produces beneficial effects in alleviating gut mucosal injury of E. coli challenged rats by enhancing the intestinal morphology and modulating cecal bacterial composition, as well as attenuating inflammatory response.

Citations

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  • Zinc Glycine supplementation improves bone quality in meat geese by modulating gut microbiota, SCFA's, and gut barrier function through Wnt10b/NF-κB axis
    Zeshan Zulfiqar, Muhammad Arslan Asif, Mengqi Liu, Shuhang Zhang, Hamid reza Rafieian Naeini, Yalei Cui, Boshuai Liu, Yinghua Shi
    Poultry Science.2025; 104(4): 104925.     CrossRef
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    Journal of Animal Science.2023;[Epub]     CrossRef
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    Research in Veterinary Science.2023; 157: 50.     CrossRef
  • Surface engineering of chitosan nanosystems and the impact of functionalized groups on the permeability of model drug across intestinal tissue
    Sadaf Ejaz, Syed Muhammad Afroz Ali, Bina Zarif, Ramla Shahid, Ayesha Ihsan, Tayyaba Noor, Muhammad Imran
    International Journal of Biological Macromolecules.2023; 242: 124777.     CrossRef
  • Chitosan Protects Immunosuppressed Mice Against Cryptosporidium parvum Infection Through TLR4/STAT1 Signaling Pathways and Gut Microbiota Modulation
    Sajid Ur Rahman, Haiyan Gong, Rongsheng Mi, Yan Huang, Xiangan Han, Zhaoguo Chen
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Effect of Dietary Zinc Methionine Supplementation on Growth Performance, Immune Function and Intestinal Health of Cherry Valley Ducks Challenged With Avian Pathogenic Escherichia coli
    Yaqi Chang, Jia Mei, Ting Yang, Zhenyu Zhang, Guangmang Liu, Hua Zhao, Xiaoling Chen, Gang Tian, Jingyi Cai, Bing Wu, Fali Wu, Gang Jia
    Frontiers in Microbiology.2022;[Epub]     CrossRef
  • Chitosan-chelated zinc modulates ileal microbiota, ileal microbial metabolites, and intestinal function in weaned piglets challenged with Escherichia coli K88
    Guojun Hou, Minyang Zhang, Jing Wang, Weiyun Zhu
    Applied Microbiology and Biotechnology.2021; 105(19): 7529.     CrossRef
  • Gut Microbiota as a Mediator of Essential and Toxic Effects of Zinc in the Intestines and Other Tissues
    Anatoly V. Skalny, Michael Aschner, Xin Gen Lei, Viktor A. Gritsenko, Abel Santamaria, Svetlana I. Alekseenko, Nagaraja Tejo Prakash, Jung-Su Chang, Elena A. Sizova, Jane C. J. Chao, Jan Aaseth, Alexey A. Tinkov
    International Journal of Molecular Sciences.2021; 22(23): 13074.     CrossRef
  • Potential Applications of Chitosan-Based Nanomaterials to Surpass the Gastrointestinal Physiological Obstacles and Enhance the Intestinal Drug Absorption
    Nutthapoom Pathomthongtaweechai, Chatchai Muanprasat
    Pharmaceutics.2021; 13(6): 887.     CrossRef
  • Modulation of Gut Microbiota for the Prevention and Treatment of COVID-19
    Jiezhong Chen, Luis Vitetta
    Journal of Clinical Medicine.2021; 10(13): 2903.     CrossRef
The putative C2H2 transcription factor RocA is a novel regulator of development and secondary metabolism in Aspergillus nidulans
Dong Chan Won , Yong Jin Kim , Da Hye Kim , Hee-Moon Park , Pil Jae Maeng
J. Microbiol. 2020;58(7):574-587.   Published online April 22, 2020
DOI: https://doi.org/10.1007/s12275-020-0083-7
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AbstractAbstract
Multiple transcriptional regulators play important roles in the coordination of developmental processes, including asexual and sexual development, and secondary metabolism in the filamentous fungus Aspergillus nidulans. In the present study, we characterized a novel putative C2H2-type transcription factor (TF), RocA, in relation to development and secondary metabolism. Deletion of rocA increased conidiation and caused defective sexual development. In contrast, the overexpression of rocA exerted opposite effects on both phenotypes. Additionally, nullifying rocA resulted in enhanced brlA expression and reduced nsdC expression, whereas its overexpression exerted the opposite effects. These results suggest that RocA functions as a negative regulator of asexual development by repressing the expression of brlA encoding a key asexual development activator, but as a positive regulator of sexual development by enhancing the expression of nsdC encoding a pivotal sexual development activator. Deletion of rocA increased the production of sterigmatocystin (ST), as well as the expression of its biosynthetic genes, aflR and stcU. Additionally, the expression of the biosynthetic genes for penicillin (PN), ipnA and acvA, and for terrequinone (TQ), tdiB and tdiE, was increased by rocA deletion. Thus, it appears that RocA functions as a negative transcriptional modulator of the secondary metabolic genes involved in ST, PN, and TQ biosynthesis. Taken together, we propose that RocA is a novel transcriptional regulator that may act either positively or negatively at multiple target genes necessary for asexual and sexual development and secondary metabolism.

Citations

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  • MtfA, a C2H2 transcriptional regulator, negatively regulates PRPS2-mediated biosynthesis of the adenosine analogue acadesine in Fusarium solani
    Qirong Chen, Jiankang Wang, Rongfei Liu, Hui Li, Zhangjiang He, Jichuan Kang
    Mycology.2025; : 1.     CrossRef
  • The hyphae-specific C 2 H 2 transcription factor HscA regulates development, stress response, and mycotoxin production in Aspergillus species
    Ye-Eun Son, Kyu-Hyun Kim, He-Jin Cho, Jae-Hyuk Yu, Hee-Soo Park, Aaron P. Mitchell
    mSphere.2025;[Epub]     CrossRef
  • Single-cell transcriptome atlas of Panax notoginseng embryonic shoot apex: Insights into developmental regulation and triterpene saponin biosynthesis
    Mei Liu, Lifang Yang, Junda Guo, Hanye Wang, Saiying Yu, Panpan Wang, Xiuming Cui, Ye Yang, Yuan Liu
    Industrial Crops and Products.2025; 235: 121820.     CrossRef
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    Scientific Reports.2023;[Epub]     CrossRef
  • Identification of a Novel Pleiotropic Transcriptional Regulator Involved in Sporulation and Secondary Metabolism Production in Chaetomium globosum
    Shanshan Zhao, Kai Zhang, Congyu Lin, Ming Cheng, Jinzhu Song, Xin Ru, Zhengran Wang, Wan Wang, Qian Yang
    International Journal of Molecular Sciences.2022; 23(23): 14849.     CrossRef
Editorial
User guides for biologists to learn computational methods
Dokyun Na
J. Microbiol. 2020;58(3):173-175.   Published online February 27, 2020
DOI: https://doi.org/10.1007/s12275-020-9723-1
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AbstractAbstract
System-wide studies of a given molecular type are referred to as “omics.” These include genomics, proteomics, and metabolomics, among others. Recent biotechnological advances allow for high-throughput measurement of cellular components, and thus it becomes possible to take a snapshot of all molecules inside cells, a form of omics study. Advances in computational modeling methods also make it possible to predict cellular mechanisms from the snapshots. These technologies have opened an era of computation-based biology. Component snapshots allow the discovery of gene-phenotype relationships in diseases, microorganisms in the human body, etc. Computational models allow us to predict new outcomes, which are useful in strain design in metabolic engineering and drug discovery from protein-ligand interactions. However, as the quantity of data increases or the model becomes complicated, the process becomes less accessible to biologists. In this special issue, six protocol articles are presented as user guides in the field of computational biology.

Citations

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  • Self-controlled in silico gene knockdown strategies to enhance the sustainable production of heterologous terpenoid by Saccharomyces cerevisiae
    Na Zhang, Xiaohan Li, Qiang Zhou, Ying Zhang, Bo Lv, Bing Hu, Chun Li
    Metabolic Engineering.2024; 83: 172.     CrossRef
  • Comparative Transcriptomic Analysis of Flagellar-Associated Genes in Salmonella Typhimurium and Its rnc Mutant
    Seungmok Han, Ji-Won Byun, Minho Lee
    Journal of Microbiology.2024; 62(1): 33.     CrossRef
  • Automation of Drug Discovery through Cutting-edge In-silico Research in Pharmaceuticals: Challenges and Future Scope
    Smita Singh, Pranjal Kumar Singh, Kapil Sachan, Mukesh Kumar, Poonam Bhardwaj
    Current Computer-Aided Drug Design.2024; 20(6): 723.     CrossRef
  • A review of Ribosome profiling and tools used in Ribo-seq data analysis
    Mingso Sherma Limbu, Tianze Xiong, Sufang Wang
    Computational and Structural Biotechnology Journal.2024; 23: 1912.     CrossRef
  • Curcumin-Incorporated Biomaterials: In silico and in vitro evaluation of biological potentials
    Nasim Azari Torbat, Iman Akbarzadeh, Niloufar Rezaei, Zahra Salehi Moghaddam, Saba Bazzazan, Ebrahim Mostafavi
    Coordination Chemistry Reviews.2023; 492: 215233.     CrossRef
  • Regulator of RNase E activity modulates the pathogenicity of Salmonella Typhimurium
    Jaejin Lee, Eunkyoung Shin, Ji-Hyun Yeom, Jaeyoung Park, Sunwoo Kim, Minho Lee, Kangseok Lee
    Microbial Pathogenesis.2022; 165: 105460.     CrossRef
  • Transcript-specific selective translation by specialized ribosomes bearing genome-encoded heterogeneous rRNAs in V. vulnificus CMCP6
    Younkyung Choi, Minju Joo, Wooseok Song, Minho Lee, Hana Hyeon, Hyun-Lee Kim, Ji-Hyun Yeom, Kangseok Lee, Eunkyoung Shin
    Journal of Microbiology.2022; 60(12): 1162.     CrossRef
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    Jang-Cheon Cho
    Journal of Microbiology.2021; 59(3): 229.     CrossRef
  • Trans-acting regulators of ribonuclease activity
    Jaejin Lee, Minho Lee, Kangseok Lee
    Journal of Microbiology.2021; 59(4): 341.     CrossRef
  • Regulator of ribonuclease activity modulates the pathogenicity of Vibrio vulnificus
    Jaejin Lee, Eunkyoung Shin, Jaeyeong Park, Minho Lee, Kangseok Lee
    Journal of Microbiology.2021; 59(12): 1133.     CrossRef
Journal Article
Machine learning methods for microbiome studies
Junghyun Namkung
J. Microbiol. 2020;58(3):206-216.   Published online February 27, 2020
DOI: https://doi.org/10.1007/s12275-020-0066-8
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AbstractAbstract
Researches on the microbiome have been actively conducted worldwide and the results have shown human gut bacterial environment significantly impacts on immune system, psychological conditions, cancers, obesity, and metabolic diseases. Thanks to the development of sequencing technology, microbiome studies with large number of samples are eligible on an acceptable cost nowadays. Large samples allow analysis of more sophisticated modeling using machine learning approaches to study relationships between microbiome and various traits. This article provides an overview of machine learning methods for non-data scientists interested in the association analysis of microbiomes and host phenotypes. Once genomic feature of microbiome is determined, various analysis
methods
can be used to explore the relationship between microbiome and host phenotypes that include penalized regression, support vector machine (SVM), random forest, and artificial neural network (ANN). Deep neural network methods are also touched. Analysis procedure from environment setup to extract analysis results are presented with Python programming language.

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