Delve into the world of the human microbiome and metagenomics
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ABSTRACT: Shotgun metagenomics provides a comprehensive snapshot of the entire microbial community present in a given environment. PreBiomics, an academic start-up of the University of Trento, employs state-of-the-art sequencing technologies and bioinformatics tools to allow the identification and characterization of the multitude of known and unknown bacteria, viruses, fungi, and other microorganisms present, shedding light on their functional capabilities, interactions, and potential impact on health or specific applications. During the talk, we will see an example of how the human microbiome is emerging as a key target of personalized medicine. BIO: Mattia Bolzan is the Chief Technology Officer in PreBiomics with more than 8 years of experience as a scientist and bioinformatician between academia and industry. He holds an MSc in Cellular and Molecular Biotechnology and through varied work experiences has developed several skills in microbiology and sequencing data analysis, specialising in computational metagenomics.
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Delve into the world of the human microbiome and metagenomics
- 1. DELVE INTO THE WORLD OF THE HUMAN MICROBIOME AND METAGENOMICS Speck&Tech 59 "Genomic Bites", 11/12/2023, Trento
- 2. Microorganisms are everywhere, from different and extreme environments 2
- 3. 3 THE HUMAN MICROBIOME Bacteria, archaea, fungi, viruses, and microeukaryotes, living in a specific human body site Prevents pathogen colonization Degrades indigestible food components Modulates the immune system
- 4. 4 MICROBIOME & HUMAN HEALTH
- 5. 5 HOW TO CHARACTERIZE THE MICROBIOME e.g., phenotypic characterization Computational analyses Isolate sequencing Limitation is that we cannot cultivate all microorganisms
- 6. 6 HOW TO CHARACTERIZE THE MICROBIOME Computational analyses Study of the whole genetic content of a sample without the need of cultivation
- 7. 7 SHOTGUN METAGENOMICS WORKFLOW Quince C, et al. Nature Biotechnology (2017)
- 8. 8 TOOLS FOR MICROBIAL PROFILING biobakery/biobakery ChocoPhlAn 3
- 9. 9 TAXONOMICAL PROFILING Genome catalog SGB organization Marker identification Taxonomic info MetaPhlAn 4 DB MetaPhlAn 4 Metagenomic samples Taxonomical profiling MetaPhlAn4 Tutorial (github.com/biobakery/MetaPhlAn/wiki/MetaPhlAn-Workshop-on-Genomics-2023) MetaPhlAn4 (github.com/biobakery/MetaPhlAn)
- 10. 10 TAXONOMICAL PROFILING Metagenome MetaPhlAn 4 Taxonomic profiled Metagenome Relative abundance Species 3 Species 2 Species 1
- 11. 11 PREBIOMICS IN A NUTSHELL Born in 2017 with a focus on dental implant clinical testing for personalized treatment, now expanding into: ▪ State-of-the-art microbiome NGS services ▪ Cutting-edge AI and bioinformatic microbiome tools ▪ Stool and skin microbiome clinical kits ▪ Revolutionary R&D on oral microbiome links with systemic disease Build a revolutionary microbiome platform for a better healthcare
- 12. 12 FROM ACADEMIC RESEARCH TO THE MARKET Foundational scientific discovery published by PreBiomics team A microbiome-based test for dentists is able to: (1) prevention, (2) early diagnosis, and (3) personalized treatment indications for peri-implant diseases
- 13. 13 PREBIOMICS IMPLANT TEST Sample collection Delivery NGS process & analysis Report Translating shotgun metagenomics workflow into a market application
- 14. 14 PREBIOMICS IMPLANT TEST PreBiomics Beta Program – The largest oral metagenomics database Italian dental clinics recruited +50 Patients recruited 1198 Peri-implant plaque & saliva samples 2441 Health & clinical parameters collected +70 Peri-implantitis 34.7% Mucositis 37.0% Healthy 28.3%
- 15. 15 HOW WE ANALYZE MICROBIOME DATA Taxonomical profiling - MetaPhlAn output
- 16. 16 HOW WE ANALYZE MICROBIOME DATA Alpha diversity • Used to measure the diversity within a sample. • Species count: the number of different species present in a sample. It does not take into account the abundance of the species or their relative distributions. Taxonomical profiling – Alpha diversity
- 17. 17 HOW WE ANALYZE MICROBIOME DATA Alpha diversity Alpha diversity in diseased samples is substantially reduced compared to healthy samples. Taxonomical profiling – Alpha diversity
- 18. 18 HOW WE ANALYZE MICROBIOME DATA Beta diversity • Used to measure the diversity between samples, e.g.: how different are two samples in microbial composition. • Bray-Curtis distance: Take into account the abundance of the species. 0 = same species at same abundance 1 = completely different species abundance Taxonomical profiling – Beta diversity
- 19. 19 HOW WE ANALYZE MICROBIOME DATA Beta diversity Healthy samples are more variable in microbial composition with respect to the diseased ones that are more defined. Taxonomical profiling – Beta diversity
- 20. 20 HOW WE ANALYZE MICROBIOME DATA Heatmaps • Useful when using large datasets • Identify if some bacteria are consistently highly abundant in one group with respect to another
- 21. Personal •Age, gender, height, weight, BMI, etc. Lifestyle •Smoking, sports Systemic health •Diabetes, autoimmune diseases, cardiovascular diseases, antibiotic usage, etc. Oral health •Parodontitis, caries, history of peri- implantitis, number of teeth left, etc. Dental implant •PPD, BoP, plaque index, suppuration, etc. 21 HOW WE ANALYZE MICROBIOME DATA Implementation of machine learning algorithms Peri-implant plaque & saliva samples 2441 Health & clinical parameters collected +70 Microbiome data Metadata
- 22. 22 HOW WE ANALYZE MICROBIOME DATA Implementation of machine learning algorithms Machine learning assesses links between the microbial features of the dental plaque samples and collected metadata
- 23. 23 HOW WE ANALYZE MICROBIOME DATA Implementation of machine learning algorithms Dental plaque microbiome has a distinctive and highly predictive signature in peri-implantitis
- 24. 24 PREBIOMICS IMPLANT TEST Application of ML algorithm in our test Development of the Peri-Implant Microbiome Score Identify peri-implantitis biomarkers before there is visible clinical manifestation of the peri-implant disease Disease prevention
- 25. 25 PREBIOMICS NGS FACILITY ▪ 10 laboratory technicians fully dedicated ▪ Semi-automated processing focused on human microbiome samples ▪ High-throughput laboratory designed to sequence up to 20,000 samples per month ▪ Dynamic and multi- disciplinary team of computational scientists
- 26. 26 THANKS FOR THE ATTENTION! Mattia Bolzan Chief Technology Officer mattia.bolzan@prebiomics.com