Requirements for Pseudomonas aeruginosa Acute Burn and Chronic Surgical Wound Infection
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{"title"=>"Requirements for Pseudomonas aeruginosa Acute Burn and Chronic Surgical Wound Infection", "type"=>"journal", "authors"=>[{"first_name"=>"Keith H.", "last_name"=>"Turner", "scopus_author_id"=>"36784020200"}, {"first_name"=>"Jake", "last_name"=>"Everett", "scopus_author_id"=>"55972629100"}, {"first_name"=>"Urvish", "last_name"=>"Trivedi", "scopus_author_id"=>"55322218800"}, {"first_name"=>"Kendra P.", "last_name"=>"Rumbaugh", "scopus_author_id"=>"6602281862"}, {"first_name"=>"Marvin", "last_name"=>"Whiteley", "scopus_author_id"=>"7007178295"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84905484563", "doi"=>"10.1371/journal.pgen.1004518", "sgr"=>"84905484563", "isbn"=>"10.1371/journal.pgen.1004518", "pmid"=>"25057820", "issn"=>"15537404", "pui"=>"373701259"}, "id"=>"f7e0bf0b-1f28-37b8-a967-f6dd61d0e51b", "abstract"=>"Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this diverse infectious capability is not accompanied by extensive variation in genomic content, suggesting that the genetic capacity to be an acute or a chronic pathogen is present in most P. aeruginosa strains. To investigate the genetic requirements for acute and chronic pathogenesis in P. aeruginosa infections, we combined high-throughput sequencing-mediated transcriptome profiling (RNA-seq) and genome-wide insertion mutant fitness profiling (Tn-seq) to characterize gene expression and fitness determinants in murine models of burn and non-diabetic chronic wound infection. Generally we discovered that expression of a gene in vivo is not correlated with its importance for fitness, with the exception of metabolic genes. By combining metabolic models generated from in vivo gene expression data with mutant fitness profiles, we determined the nutritional requirements for colonization and persistence in these infections. Specifically, we found that long-chain fatty acids represent a major carbon source in both chronic and acute wounds, and P. aeruginosa must biosynthesize purines, several amino acids, and most cofactors during infection. In addition, we determined that P. aeruginosa requires chemotactic flagellar motility for fitness and virulence in acute burn wound infections, but not in non-diabetic chronic wound infections. Our results provide novel insight into the genetic requirements for acute and chronic P. aeruginosa wound infections and demonstrate the power of using both gene expression and fitness profiling for probing bacterial virulence.", "link"=>"http://www.mendeley.com/research/requirements-pseudomonas-aeruginosa-acute-burn-chronic-surgical-wound-infection", "reader_count"=>149, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>8, "Librarian"=>1, "Researcher"=>25, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>56, "Student > Postgraduate"=>6, "Other"=>5, "Student > Master"=>13, "Student > Bachelor"=>19, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>8, "Librarian"=>1, "Researcher"=>25, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>56, "Student > Postgraduate"=>6, "Other"=>5, "Student > Master"=>13, "Student > Bachelor"=>19, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>8, "Engineering"=>4, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>25, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>74, "Medicine and Dentistry"=>9, "Physics and Astronomy"=>1, "Chemistry"=>4, "Computer Science"=>1, "Immunology and Microbiology"=>20}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>4}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Chemistry"=>{"Chemistry"=>4}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>20}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>74}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>25}, "Unspecified"=>{"Unspecified"=>8}, "Environmental Science"=>{"Environmental Science"=>2}}, "reader_count_by_country"=>{"New Zealand"=>1, "Belgium"=>1, "United States"=>4, "Taiwan"=>1, "United Kingdom"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1607489"], "description"=>"<p>(A) Log<sub>2</sub>-transformed fold change gene expression (y axis) and knockout abundance (x axis) of <i>P. aeruginosa</i> in murine burn wound infections as compared to growth in MOPS-succinate (Succ.). Significant (Sig.) changes in gene expression (fold change ≥4, P<0.01, negative binomial test) and mutant abundance (fold change ≥4, P<0.05, negative binomial test) are colored as shown (N.C., no change). (B) Spearman rank correlation coefficient between fold change expression and fold change mutant abundance in the burn wound-MOPS-succinate and the chronic wound-MOPS-succinate comparisons (x axis) for COG categories with more than 10 differentially regulated members and an associated correlation greater than 0.1 or less than −0.1 (y axis). Only genes with transposon-derived Tn-seq reads were considered.</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "knockout"], "article_id"=>1116493, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004518.g002", "stats"=>{"downloads"=>6, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genome_wide_P_aeruginosa_gene_expression_and_knockout_fitness_in_wound_infection_are_not_correlated_/1116493", "title"=>"Genome-wide <i>P. aeruginosa</i> gene expression and knockout fitness in wound infection are not correlated.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:53:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607488"], "description"=>"<p>(A) Log<sub>2</sub>-transformed differential gene expression of <i>P. aeruginosa</i> in murine burn (y axis) and chronic (x axis) wound infections as compared to growth in MOPS-succinate (Succ.). Significant changes (fold change ≥4, P<0.01, negative binomial test) are colored as shown (Diff. Exp., differentially expressed in). (B) Significantly enriched or scarce COG categories in differentially expressed gene sets (P<0.01, Fisher's exact test; †, significantly less present than expected; *, significantly more present than expected).</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "differentially", "regulates", "genes", "remodeling"], "article_id"=>1116492, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004518.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_P_aeruginosa_differentially_regulates_genes_involved_in_metabolism_motility_and_outer_surface_remodeling_in_wound_infections_/1116492", "title"=>"<i>P. aeruginosa</i> differentially regulates genes involved in metabolism, motility, and outer surface remodeling in wound infections.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:53:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607516", "https://ndownloader.figshare.com/files/1607517", "https://ndownloader.figshare.com/files/1607518", "https://ndownloader.figshare.com/files/1607519", "https://ndownloader.figshare.com/files/1607520", "https://ndownloader.figshare.com/files/1607521", "https://ndownloader.figshare.com/files/1607522", "https://ndownloader.figshare.com/files/1607523", "https://ndownloader.figshare.com/files/1607525", "https://ndownloader.figshare.com/files/1607526", "https://ndownloader.figshare.com/files/1607527"], "description"=>"<div><p>Opportunistic infections caused by <i>Pseudomonas aeruginosa</i> can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this diverse infectious capability is not accompanied by extensive variation in genomic content, suggesting that the genetic capacity to be an acute or a chronic pathogen is present in most <i>P. aeruginosa</i> strains. To investigate the genetic requirements for acute and chronic pathogenesis in <i>P. aeruginosa</i> infections, we combined high-throughput sequencing-mediated transcriptome profiling (RNA-seq) and genome-wide insertion mutant fitness profiling (Tn-seq) to characterize gene expression and fitness determinants in murine models of burn and non-diabetic chronic wound infection. Generally we discovered that expression of a gene <i>in vivo</i> is not correlated with its importance for fitness, with the exception of metabolic genes. By combining metabolic models generated from <i>in vivo</i> gene expression data with mutant fitness profiles, we determined the nutritional requirements for colonization and persistence in these infections. Specifically, we found that long-chain fatty acids represent a major carbon source in both chronic and acute wounds, and <i>P. aeruginosa</i> must biosynthesize purines, several amino acids, and most cofactors during infection. In addition, we determined that <i>P. aeruginosa</i> requires chemotactic flagellar motility for fitness and virulence in acute burn wound infections, but not in non-diabetic chronic wound infections. Our results provide novel insight into the genetic requirements for acute and chronic <i>P. aeruginosa</i> wound infections and demonstrate the power of using both gene expression and fitness profiling for probing bacterial virulence.</p></div>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "requirements", "acute", "surgical"], "article_id"=>1116500, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004518.s001", "https://dx.doi.org/10.1371/journal.pgen.1004518.s002", "https://dx.doi.org/10.1371/journal.pgen.1004518.s003", "https://dx.doi.org/10.1371/journal.pgen.1004518.s004", "https://dx.doi.org/10.1371/journal.pgen.1004518.s005", "https://dx.doi.org/10.1371/journal.pgen.1004518.s006", "https://dx.doi.org/10.1371/journal.pgen.1004518.s007", "https://dx.doi.org/10.1371/journal.pgen.1004518.s008", "https://dx.doi.org/10.1371/journal.pgen.1004518.s009", "https://dx.doi.org/10.1371/journal.pgen.1004518.s010", "https://dx.doi.org/10.1371/journal.pgen.1004518.s011"], "stats"=>{"downloads"=>19, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Requirements_for_Pseudomonas_aeruginosa_Acute_Burn_and_Chronic_Surgical_Wound_Infection/1116500", "title"=>"Requirements for <i>Pseudomonas aeruginosa</i> Acute Burn and Chronic Surgical Wound Infection", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-24 02:53:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607493"], "description"=>"<p>(A) Fold change mutant abundance in murine wound infections as compared to MOPS-succinate (Succ.) is shown for genes involved in chemotaxis (*, P<0.05, negative binomial test). (B) Log<sub>2</sub>-transformed fold change gene expression (y axis) and knockout abundance (x axis) of <i>P. aeruginosa</i> in murine chronic wound infections as compared to murine burn wound infections. Significant changes in knockout abundance (fold change ≥4, P<0.05, negative binomial test) are colored purple, and genes annotated as being involved in flagellar assembly or bacterial chemotaxis in the KEGG PATHWAYS database are highlighted green and red, respectively (N.C., no change). (C) Kaplan-Meier survival curves of burned mice infected with wild-type PAO1, a <i>cheR1</i> transposon mutant derivative (<i>cheR1</i>::Tn), or an unmarked, in-frame <i>cheR1</i> deletion mutant (Δ<i>cheR1</i>). The experiment was performed twice (PAO1, <i>cheR1</i>::Tn) or once (Δ<i>cheR1</i>), with three to five mice per group, and the percent survival of all mice is shown (*, P<0.01, log-rank (Mantel-Cox) test; n = 8 (PAO1), n = 9 (<i>cheR1</i>::Tn), n = 5 (Δ<i>cheR1</i>)). (D) Growth of wild-type PAO1 or a <i>cheR1</i> transposon mutant derivative in murine chronic wounds four days post infection. Each symbol represents a value obtained from infection of an individual mouse. The central bar indicates the mean, and error bars indicate standard error of the mean. No significant difference was observed (P = 0.194, unpaired T-test).</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "flagellar", "motility", "wounds"], "article_id"=>1116497, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004518.g006", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Chemotactic_flagellar_motility_is_required_in_burn_wounds_and_not_chronic_wounds_/1116497", "title"=>"Chemotactic flagellar motility is required in burn wounds and not chronic wounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:53:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607491"], "description"=>"<p>(A) Fold change gene expression (above) or mutant abundance (below) in murine wound infections as compared to MOPS-succinate (Succ.) is shown for the long-chain fatty acid oxidation genes <i>faoAB</i> (*, P<0.05, negative binomial test; †, P<0.01, negative binomial test) (B) Kaplan-Meier survival curves of burned mice infected with wild-type PAO1, an <i>faoA</i> transposon mutant derivative (<i>faoA</i>::Tn), or an unmarked, in-frame <i>faoA</i> deletion mutant (Δ<i>faoA</i>). The experiment was performed twice (PAO1, <i>faoA</i>::Tn) or once (Δ<i>faoA</i>), with three to five mice per group, and the percent survival of all mice is shown (*, P<0.005, log-rank (Mantel-Cox) test; n = 8 (PAO1), n = 10 (<i>faoA</i>::Tn), n = 5 (Δ<i>faoA</i>)). (C) Growth of wild-type PAO1, <i>faoA</i>::Tn, or Δ<i>faoA</i> in murine chronic wounds four days post infection. Each symbol represents a value obtained from infection of an individual mouse. The central bar indicates the mean, and error bars indicate standard error of the mean (*, P = 0.023, unpaired T-test; †, P = 0.091, unpaired T-test).</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "fatty", "oxidation", "virulence"], "article_id"=>1116495, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004518.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Long_chain_fatty_acid_oxidation_is_required_for_P_aeruginosa_virulence_and_fitness_in_wounds_/1116495", "title"=>"Long-chain fatty acid oxidation is required for <i>P. aeruginosa</i> virulence and fitness in wounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:53:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607492"], "description"=>"<p>(A) <i>P. aeruginosa</i> must biosynthesize several amino acids, cofactors, and metabolic endproducts during growth <i>in vivo</i>. If mutants in >33% of genes predicted to be in the biosynthetic pathway of a given metabolite were more fit in both burn and chronic wounds than in MOPS-Succ (fold change ≥2, P<0.05, negative binomial test), that metabolite was said to be “Available” to <i>P. aeruginosa in vivo</i>. If 5–33% of genes predicted to be in the biosynthetic pathway of a given metabolite were more fit in both burn and chronic wounds than in MOPS-Succ, or if only one infection matched the criteria for “Available” as described above, that metabolite was said to be “Potentially Available”. If <5% of genes predicted to be in the biosynthetic pathway of a given metabolite were more fit in both burn and chronic wounds than in MOPS-Succ, that metabolite was said to be “Not Available”. Genes predicted to be involved in synthesis of necessary metabolites were identified from the PseudoCyc database (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004518#pgen.1004518.s010\" target=\"_blank\">Table S7</a> for details). (B) Kaplan-Meier survival curves of burned mice infected with PAO1 Δ<i>pabC</i>, PAO1 Δ<i>purF</i>, PAO1 Δ<i>hisE</i>, or PAO1 Δ<i>ilvD</i>. The first two strains are auxotrophic for metabolites predicted to be not available, and the last two strains are auxotrophic for metabolites predicted to be available. The experiment was performed with five mice per group, and the percent survival of all mice is shown (*, P<0.05, log-rank (Mantel-Cox) test).</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "requirements"], "article_id"=>1116496, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004518.g005", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Biosynthetic_requirements_of_P_aeruginosa_during_wound_infection_/1116496", "title"=>"Biosynthetic requirements of <i>P. aeruginosa</i> during wound infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:53:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607490"], "description"=>"<p>Metabolic steps as identified by KEGG Orthology are colored according to their relative expression in both burn and chronic wounds as compared to growth in MOPS-succinate (Succ.). Only significant changes (fold change ≥4, P<0.01, negative binomial test) in both burn and chronic wounds are shown. Pathways and metabolic steps of interest are highlighted in yellow, and succinate, the sole carbon and energy source in the control medium, is indicated with an arrow. Generally, biosynthetic pathways were down-regulated and anaplerotic pathways were up-regulated <i>in vivo</i>. (PEPC, PEP carboxylase; THF; tetrahydrofolate).</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "metabolism", "rna-seq"], "article_id"=>1116494, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004518.g003", "stats"=>{"downloads"=>5, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reconstruction_of_in_vivo_metabolism_from_RNA_seq_data_/1116494", "title"=>"Reconstruction of <i>in vivo</i> metabolism from RNA-seq data.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-24 02:53:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1607494"], "description"=>"1<p>Spearman rank correlation coefficient between fold change expression and fold change mutant abundance. More negative indicates a greater fitness contribution by up-regulated genes and/or a lesser fitness contribution by down-regulated genes.</p>2<p>Number of genes considered is shown in parentheses.</p>3<p>Differentially expressed (fold change ≥4, P<0.01, negative binomial test).</p>4<p>Enzyme Commission.</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Transcriptome analysis", "Genome expression analysis", "genetics", "gene expression", "genomics", "microbiology", "bacteriology", "Bacterial physiology", "Gram negative bacteria", "Medical microbiology", "Microbial pathogens", "Bacterial pathogens", "Microbial physiology", "Microbial metabolism", "systems biology", "Model organisms", "Animal models", "Mouse models", "mutant", "poorly"], "article_id"=>1116498, "categories"=>["Biological Sciences"], "users"=>["Keith H. Turner", "Jake Everett", "Urvish Trivedi", "Kendra P. Rumbaugh", "Marvin Whiteley"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004518.t001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_expression_and_mutant_fitness_are_poorly_correlated_/1116498", "title"=>"Differential expression and mutant fitness are poorly correlated.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-24 02:53:10"}

PMC Usage Stats | Further Information

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Relative Metric

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