Limits...
Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma.

Pérez-Losada M, Castro-Nallar E, Bendall ML, Freishtat RJ, Crandall KA - PLoS ONE (2015)

Bottom Line: Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation.Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested.Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology Institute, George Washington University, Ashburn, Virginia, United States of America; Division of Emergency Medicine, Children's National Medical Center, Washington, DC, United States of America; CIBIO-InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Vairão, Portugal.

ABSTRACT

Background: High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for variation in clinical metadata.

Methods: Transcriptomic (host) and metatranscriptomic (microbiota) sequences from the nasal epithelium of 8 asthmatics and 6 healthy controls were separated in silico and mapped to available human and NCBI-NR protein reference databases. Human genes differentially expressed in asthmatics and controls were then used to infer upstream regulators involved in immune and inflammatory responses. Concomitantly, microbial genes were mapped to metabolic databases (COG, SEED, and KEGG) to infer microbial functions differentially expressed in asthmatics and controls. Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation.

Results and discussion: Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested. Enrichment analysis of 499 differentially expressed host genes for inflammatory and immune responses revealed 43 upstream regulators differentially activated in asthma. Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.

No MeSH data available.


Related in: MedlinePlus

Ingenuity pathway enrichment analyses to detect upstream regulators associated with the inflammatory and immune responses during asthma.The activation z-score depicts the degree of activation or suppression of a given regulator.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4488395&req=5

pone.0131819.g002: Ingenuity pathway enrichment analyses to detect upstream regulators associated with the inflammatory and immune responses during asthma.The activation z-score depicts the degree of activation or suppression of a given regulator.

Mentions: Our transcriptomic analyses identified 499 (324 up-regulated and 175 down-regulated) core asthma genes differentially expressed (P < 0.003; log-fold-change ≥1.5) in the epithelial cells of asthmatic and non-asthmatic patients (S2 Table). Both were fully separated based on the abundances of the most differentially expressed (log-fold-change ≥3) 79 host genes (Fig 1). The core asthma signature (499 genes) was then loaded into IPA and enriched for genes connected to upstream regulator molecules related to inflammatory and immune responses during asthma [46–59]. Regulators were classified by group, including: complex, cytokine, group, growth factor, transcription regulator, chemical and other molecules. Four and 39 regulators were predicted to be inhibited (z-score ≤-2; P value range: 6.7E-05 to 2.9E-15) and activated (z-score ≥2; P value range: 1.9E-02 to 8.5E-50), respectively (Fig 2).


Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma.

Pérez-Losada M, Castro-Nallar E, Bendall ML, Freishtat RJ, Crandall KA - PLoS ONE (2015)

Ingenuity pathway enrichment analyses to detect upstream regulators associated with the inflammatory and immune responses during asthma.The activation z-score depicts the degree of activation or suppression of a given regulator.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488395&req=5

pone.0131819.g002: Ingenuity pathway enrichment analyses to detect upstream regulators associated with the inflammatory and immune responses during asthma.The activation z-score depicts the degree of activation or suppression of a given regulator.
Mentions: Our transcriptomic analyses identified 499 (324 up-regulated and 175 down-regulated) core asthma genes differentially expressed (P < 0.003; log-fold-change ≥1.5) in the epithelial cells of asthmatic and non-asthmatic patients (S2 Table). Both were fully separated based on the abundances of the most differentially expressed (log-fold-change ≥3) 79 host genes (Fig 1). The core asthma signature (499 genes) was then loaded into IPA and enriched for genes connected to upstream regulator molecules related to inflammatory and immune responses during asthma [46–59]. Regulators were classified by group, including: complex, cytokine, group, growth factor, transcription regulator, chemical and other molecules. Four and 39 regulators were predicted to be inhibited (z-score ≤-2; P value range: 6.7E-05 to 2.9E-15) and activated (z-score ≥2; P value range: 1.9E-02 to 8.5E-50), respectively (Fig 2).

Bottom Line: Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation.Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested.Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology Institute, George Washington University, Ashburn, Virginia, United States of America; Division of Emergency Medicine, Children's National Medical Center, Washington, DC, United States of America; CIBIO-InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, Vairão, Portugal.

ABSTRACT

Background: High-throughput sequencing (HTS) analysis of microbial communities from the respiratory airways has heavily relied on the 16S rRNA gene. Given the intrinsic limitations of this approach, airway microbiome research has focused on assessing bacterial composition during health and disease, and its variation in relation to clinical and environmental factors, or other microbiomes. Consequently, very little effort has been dedicated to describing the functional characteristics of the airway microbiota and even less to explore the microbe-host interactions. Here we present a simultaneous assessment of microbiome and host functional diversity and host-microbe interactions from the same RNA-seq experiment, while accounting for variation in clinical metadata.

Methods: Transcriptomic (host) and metatranscriptomic (microbiota) sequences from the nasal epithelium of 8 asthmatics and 6 healthy controls were separated in silico and mapped to available human and NCBI-NR protein reference databases. Human genes differentially expressed in asthmatics and controls were then used to infer upstream regulators involved in immune and inflammatory responses. Concomitantly, microbial genes were mapped to metabolic databases (COG, SEED, and KEGG) to infer microbial functions differentially expressed in asthmatics and controls. Finally, multivariate analysis was applied to find associations between microbiome characteristics and host upstream regulators while accounting for clinical variation.

Results and discussion: Our study showed significant differences in the metabolism of microbiomes from asthmatic and non-asthmatic children for up to 25% of the functional properties tested. Enrichment analysis of 499 differentially expressed host genes for inflammatory and immune responses revealed 43 upstream regulators differentially activated in asthma. Microbial adhesion (virulence) and Proteobacteria abundance were significantly associated with variation in the expression of the upstream regulator IL1A; suggesting that microbiome characteristics modulate host inflammatory and immune systems during asthma.

No MeSH data available.


Related in: MedlinePlus