The Identification of Circulating MiRNA in Bovine Serum and Their Potential as Novel Biomarkers of Early Mycobacterium avium subsp paratuberculosis Infection
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{"title"=>"The identification of circulating MiRNA in bovine serum and their potential as novel biomarkers of early mycobacterium avium subsp paratuberculosis infection", "type"=>"journal", "authors"=>[{"first_name"=>"Damien", "last_name"=>"Farrell", "scopus_author_id"=>"35738450700"}, {"first_name"=>"Ronan G.", "last_name"=>"Shaughnessy", "scopus_author_id"=>"56845152400"}, {"first_name"=>"Louise", "last_name"=>"Britton", "scopus_author_id"=>"56845069900"}, {"first_name"=>"David E.", "last_name"=>"MacHugh", "scopus_author_id"=>"6602729818"}, {"first_name"=>"Bryan", "last_name"=>"Markey", "scopus_author_id"=>"7004318666"}, {"first_name"=>"Stephen V.", "last_name"=>"Gordon", "scopus_author_id"=>"7401828865"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"605997057", "sgr"=>"84941710757", "issn"=>"19326203", "pmid"=>"26218736", "scopus"=>"2-s2.0-84941710757", "doi"=>"10.1371/journal.pone.0134310", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)"}, "id"=>"b397c531-62d3-3f52-9eb2-9d998ef4a01c", "abstract"=>"Mycobacterium avium subspecies paratuberculosis (MAP) is the aetiological agent of Johne's disease (JD), a chronic enteritis in ruminants that causes substantial economic loses to agriculture worldwide. Current diagnostic assays are hampered by low sensitivity and specificity that seriously complicate disease control; a new generation of diagnostic and prognostic assays are therefore urgently needed. Circulating microRNAs (miRNAs) have been shown to have significant potential as novel biomarkers for a range of human diseases, but their potential application in the veterinary sphere has been less well characterised. The aim of this study was therefore to apply RNA-sequencing approaches to serum from an experimental JD infection model as a route to identify novel diagnostic and prognostic miRNA biomarkers. Sera from experimental MAP-challenged calves (n = 6) and age-matched controls (n = 6) were used. We identified a subset of known miRNAs from bovine serum across all samples, with approximately 90 being at potentially functional abundance levels. The majority of known bovine miRNAs displayed multiple isomiRs that differed from the canonical sequences. Thirty novel miRNAs were identified after filtering and were found within sera from all animals tested. No significant differential miRNA expression was detected when comparing sera from MAP-challenged animals to their age-matched controls at six-month's post-infection. However, comparing sera from pre-infection bleeds to six-month's post-infection across all 12 animals did identify increased miR-205 (2-fold) and decreased miR-432 (2-fold) within both challenged and control groups, which suggests changes in circulating miRNA profiles due to ageing or development (P<0.00001). In conclusion our study has identified a range of novel miRNA in bovine serum, and shown the utility of small RNA sequencing approaches to explore the potential of miRNA as novel biomarkers for infectious disease in cattle.", "link"=>"http://www.mendeley.com/research/identification-circulating-mirna-bovine-serum-potential-novel-biomarkers-early-mycobacterium-avium-s", "reader_count"=>19, "reader_count_by_academic_status"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>1, "Veterinary Science and Veterinary Medicine"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>2}}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2192185"], "description"=>"<p>Normalised read variation for differentially abundant genes from 0–6 months in both control (blue) and infected (green) groups. The bars on each point represent the within group variation for 6 animals (95% confidence interval).</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495872, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.g007", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_expression_results_/1495872", "title"=>"Differential expression results.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192183"], "description"=>"<p>A: The relative frequencies of all isomiR classes including exact matches to the reference. <i>nta#*</i> denote non-templated additions, <i>lv3p</i> and <i>lv5p</i> the 5' and 3' length variants and <i>mv</i> denotes variants different at both ends. Classification is according to the sRNAbench hierarchical scheme. B: Length distributions for 5' and 3' variants showing the large variation in the latter. (x-axis shows length difference from canonical form). A number of the extreme 3' trimmed sequences are possibly due to erroneous mapping of short reads <18nt.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495870, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.g005", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Isomir_results_/1495870", "title"=>"Isomir results.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192180"], "description"=>"<p>A: Proportion of reads mapped to different small RNAs. Values are the average percentage over all samples. Reads matching tRNA dominate. The unmapped percentage is likely due to mismatches in the reads or unannotated ncRNAs. B: Variation of known miRNA discovered with increasing random reads for both methods used in this study. sRNAbench is more sensitive to low abundance genes and produces more hits at a given file size. miRDeep2 was run with no score cut-off. Discovery tails off at 4 million reads in both methods. The inset plot shows the mean abundance of each newly discovered set, illustrating that only low abundance miRNAs are being added after ~3 million mark. C: Overlap between the top 80 miRDeep and sRNAbench results for known miRNAs shows almost identical results. D: Correlation between total read counts determined by both methods for the overlapping miRNAs.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495867, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.g002", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miRNA_abundances_in_miRDeep2_and_sRNAbench_/1495867", "title"=>"miRNA abundances in miRDeep2 and sRNAbench.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192179"], "description"=>"<p>IFN-<b>γ</b> production in control (n = 20) and MAP-challenged (n = 20) cattle at 2 months and 6 months post-infection in whole blood in response to PPD-J. Each point represents an individual animal while the red points indicate the six MAP-challenged cattle selected for miRNA-sequencing. The horizontal lines represent mean OD<sub>450</sub> values for each plot.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495866, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Responses_to_PPD_J_in_both_sets_of_animals_/1495866", "title"=>"Responses to PPD-J in both sets of animals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192188"], "description"=>"<p>Differentially expressed miRNA identified by comparing time-point 0 to time-point 6 months within each group (MAP-infected versus controls).</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495875, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.t003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_expressed_miRNA_identified_by_comparing_time_point_0_to_time_point_6_months_within_each_group_MAP_infected_versus_controls_/1495875", "title"=>"Differentially expressed miRNA identified by comparing time-point 0 to time-point 6 months within each group (MAP-infected versus controls).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192187"], "description"=>"<p>The 'gene' column denotes a host gene where found with transcription unit (intron or exon). The table is sorted by conservation in mammal species, that is, the number of species with aligned orthologs (aligned column). tr. unit = transcription unit. *max identity is the highest sequence identity to another species.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495874, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.t002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Novel_micro_RNAs_predicted_in_the_data_by_mirDeep2_after_filtering_steps_/1495874", "title"=>"Novel micro RNAs predicted in the data by mirDeep2 (after filtering steps).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192182"], "description"=>"<p>The known bovine miRnome from miRBase 1.2 is in red. The green set are currently annotated extracellular circulating miRNA human families from the miRandola database. The yellow set represents our core bovine miRNAs.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495869, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overlap_between_core_miRNAs_in_this_study_and_known_databases_/1495869", "title"=>"Overlap between core miRNAs in this study and known databases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192181"], "description"=>"<p>Read count distributions in all samples for top known miRNAs found by miRDeep2.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495868, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Read_count_distributions_in_all_samples_for_top_known_miRNAs_found_by_miRDeep2_/1495868", "title"=>"Read count distributions in all samples for top known miRNAs found by miRDeep2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192189", "https://ndownloader.figshare.com/files/2192190", "https://ndownloader.figshare.com/files/2192191", "https://ndownloader.figshare.com/files/2192192", "https://ndownloader.figshare.com/files/2192193", "https://ndownloader.figshare.com/files/2192194", "https://ndownloader.figshare.com/files/2192195", "https://ndownloader.figshare.com/files/2192196", "https://ndownloader.figshare.com/files/2192197", "https://ndownloader.figshare.com/files/2192198", "https://ndownloader.figshare.com/files/2192199"], "description"=>"<div><p><i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP) is the aetiological agent of Johne’s disease (JD), a chronic enteritis in ruminants that causes substantial economic loses to agriculture worldwide. Current diagnostic assays are hampered by low sensitivity and specificity that seriously complicate disease control; a new generation of diagnostic and prognostic assays are therefore urgently needed. Circulating microRNAs (miRNAs) have been shown to have significant potential as novel biomarkers for a range of human diseases, but their potential application in the veterinary sphere has been less well characterised. The aim of this study was therefore to apply RNA-sequencing approaches to serum from an experimental JD infection model as a route to identify novel diagnostic and prognostic miRNA biomarkers. Sera from experimental MAP-challenged calves (n = 6) and age-matched controls (n = 6) were used. We identified a subset of known miRNAs from bovine serum across all samples, with approximately 90 being at potentially functional abundance levels. The majority of known bovine miRNAs displayed multiple isomiRs that differed from the canonical sequences. Thirty novel miRNAs were identified after filtering and were found within sera from all animals tested. No significant differential miRNA expression was detected when comparing sera from MAP-challenged animals to their age-matched controls at six-month’s post-infection. However, comparing sera from pre-infection bleeds to six-month’s post-infection across all 12 animals did identify increased miR-205 (2-fold) and decreased miR-432 (2-fold) within both challenged and control groups, which suggests changes in circulating miRNA profiles due to ageing or development (P<0.00001). In conclusion our study has identified a range of novel miRNA in bovine serum, and shown the utility of small RNA sequencing approaches to explore the potential of miRNA as novel biomarkers for infectious disease in cattle.</p></div>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495876, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0134310.s001", "https://dx.doi.org/10.1371/journal.pone.0134310.s002", "https://dx.doi.org/10.1371/journal.pone.0134310.s003", "https://dx.doi.org/10.1371/journal.pone.0134310.s004", "https://dx.doi.org/10.1371/journal.pone.0134310.s005", "https://dx.doi.org/10.1371/journal.pone.0134310.s006", "https://dx.doi.org/10.1371/journal.pone.0134310.s007", "https://dx.doi.org/10.1371/journal.pone.0134310.s008", "https://dx.doi.org/10.1371/journal.pone.0134310.s009", "https://dx.doi.org/10.1371/journal.pone.0134310.s010", "https://dx.doi.org/10.1371/journal.pone.0134310.s011"], "stats"=>{"downloads"=>5, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Identification_of_Circulating_MiRNA_in_Bovine_Serum_and_Their_Potential_as_Novel_Biomarkers_of_Early_Mycobacterium_avium_subsp_paratuberculosis_Infection/1495876", "title"=>"The Identification of Circulating MiRNA in Bovine Serum and Their Potential as Novel Biomarkers of Early <i>Mycobacterium avium</i> subsp <i>paratuberculosis</i> Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192186"], "description"=>"<p>Those not marked as 'exact' variants are different from the canonical miRBase sequence. Variants are named using the sRNAbench nomenclature.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495873, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.t001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Top_20_dominant_isomiRs_across_all_samples_/1495873", "title"=>"Top 20 dominant isomiRs across all samples.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-07-28 03:10:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/2192184"], "description"=>"<p>Predicted RNA secondary structure of the hairpin for novel micro RNAs. Sequence is coloured according to mature (red) and star (green). Sequences are consensus derived by miRDeep2.</p>", "links"=>[], "tags"=>["prognostic miRNA biomarkers", "novel biomarkers", "JD infection model", "RNA sequencing approaches", "Mycobacterium avium subsp paratuberculosis Infection Mycobacterium avium subspecies paratuberculosis"], "article_id"=>1495871, "categories"=>["Biological Sciences"], "users"=>["Damien Farrell", "Ronan G. Shaughnessy", "Louise Britton", "David E. MacHugh", "Bryan Markey", "Stephen V. Gordon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134310.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selected_novel_miRNAs_/1495871", "title"=>"Selected novel miRNAs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-07-28 03:10:59"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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