scholarly journals Improving characterization of understudied human microbiomes using targeted phylogenetics

2019 ◽  
Author(s):  
Bruce A Rosa ◽  
Kathie Mihindukulasuriya ◽  
Kymberlie Hallsworth-Pepin ◽  
Aye Wollam ◽  
John Martin ◽  
...  

AbstractWhole genome bacterial sequences are required to better understand microbial functions, niches-pecific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g. stool), as few as 13% of bacterial-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from under-represented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full length 16S rRNA sequences, clustered the sequences to ensure that no individual taxonomic group was over-selected for sequencing, prioritized bacteria from under-represented body sites (such as skin, respiratory and urinary tract), and sequenced and assembled genomes for 665 new bacterial strains. Here we show that addition of these genomes improved read mapping rates of HMP metagenomic samples by nearly 30% for the previously under-represented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and clinical perspective.ImportanceThe human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily stool), while other sites such as the skin, respiratory tract and urinary tracts are under-represented, resulting in as little as 13% of bacterial-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select under-represented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.

mSystems ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Bruce A. Rosa ◽  
Kathie Mihindukulasuriya ◽  
Kymberlie Hallsworth-Pepin ◽  
Aye Wollam ◽  
John Martin ◽  
...  

ABSTRACT Whole-genome bacterial sequences are required to better understand microbial functions, niche-specific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g., feces), as few as 13% of bacterium-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from underrepresented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full-length 16S rRNA gene sequences, clustered the sequences to ensure that no individual taxonomic group was overselected for sequencing, prioritized bacteria from underrepresented body sites (such as skin and respiratory and urinary tracts), and sequenced and assembled genomes for 665 new bacterial strains. Here, we show that addition of these genomes improved read mapping rates of Human Microbiome Project (HMP) metagenomic samples by nearly 30% for the previously underrepresented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and a clinical perspective. IMPORTANCE The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily feces), while other sites such as the skin, respiratory tract, and urinary tract are underrepresented, resulting in as little as 13% of bacterium-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select underrepresented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.


2020 ◽  
Vol 3 (1) ◽  
pp. 411-432
Author(s):  
Chengsheng Zhu ◽  
Maximilian Miller ◽  
Zishuo Zeng ◽  
Yanran Wang ◽  
Yannick Mahlich ◽  
...  

The past two decades of analytical efforts have highlighted how much more remains to be learned about the human genome and, particularly, its complex involvement in promoting disease development and progression. While numerous computational tools exist for the assessment of the functional and pathogenic effects of genome variants, their precision is far from satisfactory, particularly for clinical use. Accumulating evidence also suggests that the human microbiome's interaction with the human genome plays a critical role in determining health and disease states. While numerous microbial taxonomic groups and molecular functions of the human microbiome have been associated with disease, the reproducibility of these findings is lacking. The human microbiome–genome interaction in healthy individuals is even less well understood. This review summarizes the available computational methods built to analyze the effect of variation in the human genome and microbiome. We address the applicability and precision of these methods across their possible uses. We also briefly discuss the exciting, necessary, and now possible integration of the two types of data to improve the understanding of pathogenicity mechanisms.


2017 ◽  
Author(s):  
Victoria Cepeda ◽  
Bo Liu ◽  
Mathieu Almeida ◽  
Christopher M. Hill ◽  
Sergey Koren ◽  
...  

ABSTRACTMetagenomic studies have primarily relied on de novo approaches for reconstructing genes and genomes from microbial mixtures. While database driven approaches have been employed in certain analyses, they have not been used in the assembly of metagenomes. Here we describe the first effective approach for reference-guided metagenomic assembly of low-abundance bacterial genomes that can complement and improve upon de novo metagenomic assembly methods. When combined with de novo assembly approaches, we show that MetaCompass can generate more complete assemblies than can be obtained by de novo assembly alone, and improve on assemblies from the Human Microbiome Project (over 2,000 samples).


2020 ◽  
Author(s):  
Chan Wang ◽  
Jiyuan Hu ◽  
Martin J. Blaser ◽  
Huilin Li

AbstractMotivationThe human microbiome is inherently dynamic and its dynamic nature plays a critical role in maintaining health and driving disease. With an increasing number of longitudinal microbiome studies, scientists are eager to learn the comprehensive characterization of microbial dynamics and their implications to the health and disease-related phenotypes. However, due to the challenging structure of longitudinal microbiome data, few analytic methods are available to characterize the microbial dynamics over time.ResultsWe propose a microbial trend analysis (MTA) framework for the high-dimensional and phylogenetically-based longitudinal microbiome data. In particular, MTA can perform three tasks: 1) capture the common microbial dynamic trends for a group of subjects on the community level and identify the dominant taxa; 2) examine whether or not the microbial overall dynamic trends are significantly different in groups; 3) classify an individual subject based on its longitudinal microbial profiling. Our extensive simulations demonstrate that the proposed MTA framework is robust and powerful in hypothesis testing, taxon identification, and subject classification. Our real data analyses further illustrate the utility of MTA through a longitudinal study in mice.ConclusionsThe proposed MTA framework is an attractive and effective tool in investigating dynamic microbial pattern from longitudinal microbiome studies.


2017 ◽  
Vol 200 (3) ◽  
Author(s):  
Celia Méndez-García ◽  
Coral Barbas ◽  
Manuel Ferrer ◽  
David Rojo

ABSTRACT In 1680, Antonie van Leeuwenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leeuwenhoek's time to successful modern attempts at changing the gut microbial landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune systems, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa and some of their functional molecules (i.e., genes, proteins, and metabolites) with health and disease states. Nevertheless, misleading experimental design on human subjects and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins and metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial product imbalances that relate to disease and health.


2022 ◽  
Vol 23 (1) ◽  
pp. 483
Author(s):  
Vasily A. Popkov ◽  
Anastasia A. Zharikova ◽  
Evgenia A. Demchenko ◽  
Nadezda V. Andrianova ◽  
Dmitry B. Zorov ◽  
...  

Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as “uremic toxins”. The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.


Author(s):  
Natasha R.F. Novaes ◽  
Isabel C. M. Fensterseifer ◽  
José L. R. Martins ◽  
Osmar N. Silva

Forensic Science compounds many study areas in context of solving crimes, one of which is the forensic microbiology. Combined with genomic approaches, microbiology has shown strong performance in studies regarding the relationship between microorganisms present on human skin and environment. The Human Microbiome Project (HMP) has contributed significantly to characterization of microbial complexity and their connection to human being. The purpose of this work consists of a historical overview of scientific articles, demonstrating the growth and possibility of using skin microbiome in forensic identification. Studies about use of cutaneous microbiome in human identification, as well its forensic approaches, were looked into for writing of this review. Comparisons among cutaneous microbial communities and manipulated objects have been tested using 16S rRNA, as well as a thorough sequencing of the bacterial genome. From use of ecological measures of distance to genetic markers with nucleotide variants and predictive algorithms, research has shown promising results for advances in field of forensic identification. The development of metagenomic microbial panel markers, named hidSkinPlax for targeted sequencing has been designed and tested with great results. Research results show satisfactory potential in human identification by cutaneous microbiome and the possibility for contributive use in elucidating crimes.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4357
Author(s):  
Michal Styczynski ◽  
Agata Rogowska ◽  
Katarzyna Gieczewska ◽  
Maciej Garstka ◽  
Anna Szakiel ◽  
...  

Antarctic regions are characterized by low temperatures and strong UV radiation. This harsh environment is inhabited by psychrophilic and psychrotolerant organisms, which have developed several adaptive features. In this study, we analyzed two Antarctic bacterial strains, Planococcus sp. ANT_H30 and Rhodococcus sp. ANT_H53B. The physiological analysis of these strains revealed their potential to produce various biotechnologically valuable secondary metabolites, including surfactants, siderophores, and orange pigments. The genomic characterization of ANT_H30 and ANT_H53B allowed the identification of genes responsible for the production of carotenoids and the in silico reconstruction of the pigment biosynthesis pathways. The complex manual annotation of the bacterial genomes revealed the metabolic potential to degrade a wide variety of compounds, including xenobiotics and waste materials. Carotenoids produced by these bacteria were analyzed chromatographically, and we proved their activity as scavengers of free radicals. The quantity of crude carotenoid extracts produced at two temperatures using various media was also determined. This was a step toward the optimization of carotenoid production by Antarctic bacteria on a larger scale.


2015 ◽  
Vol 61 (2) ◽  
pp. 90-94 ◽  
Author(s):  
Mor Nitzan ◽  
Sefi Mintzer ◽  
Hanah Margalit

The human microbiome is dynamic and unique to each individual, and its role is being increasingly recognized in healthy physiology and in disease, including gastrointestinal and neuropsychiatric disorders. Therefore, characterizing the human microbiome and the factors that shape its bacterial population, how they are related to host-specific attributes, and understanding the ways in which it can be manipulated and the phenotypic consequences of such manipulations are of great importance. Characterization of the microbiome so far has been mostly based on compositional studies alone, where relative abundances of different species are compared in different conditions, such as health and disease. However, inter-relationships among the bacterial species, such as competition and cooperation over metabolic resources, may be an important factor that affects the structure and function of the microbiome. Here we review the network-based approaches in answering such questions and explore the first attempts that focus on the interactions facet, complementing compositional studies, towards understanding the microbiome structure and its complex relationship with the human host.


2020 ◽  
Author(s):  
Eiphrangdaka L. Suchiang ◽  
Deepak Kumar ◽  
Shabana Yeasmin ◽  
Monisha Singh ◽  
James Michael ◽  
...  

AbstractThe Human Microbiome Project (HMP) launched in 2008 by the National Institute of Health (NIH) fascinated microbiologists with discoveries of micro-organisms inside and outside of human beings. Their correlation with health and disease brings a new insight to preventive and therapeutic measures. At present, focus is more on the micro-organisms residing in the gut and various factors capable of altering their composition. The conclusion made by Dr. Edward Bach regarding the ability of homoeopathic potencies to alter bowel flora and its relation with chronic diseases was investigated and experimented way back. The present review attempts to correlate gut microbiota with the art and science of homoeopathy.


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