CalCEN: A Co-Expression Network for Candida albicans

Elucidating gene function is a major goal in biology, especially among non-model organisms. However, doing so is complicated by the fact that molecular conservation does not always mirror functional conservation, and that complex relationships among genes are responsible for encoding pathways and higher-order biological processes. Co-expression, a promising approach for predicting gene function, relies on the general principle that genes with similar expression patterns across multiple conditions will likely be involved in the same biological process. For Candida albicans, a prevalent human fungal pathogen, we leveraged a large amount of publicly available transcriptomic data to generate a C. albicans Co-Expression Network (CalCEN), recapitulating known protein networks, predicting gene function, and enabling insights into the principles influencing co-expression. Overall, co-expression is a powerful tool for uncovering gene function, and decreases the experimental tests needed to identify functions for currently under-annotated genes.

Reference:

TR O'Meara, MJ O'Meara, M Sphere, 2020
DeORFanizing Candida albicans Genes using Co-Expression

Code available at: http://github.com/momeara/CalCEN

Candida albicans Co-Expression Network (CalCEN) version 1.0.0

Files

chromsome_features.tsv

• Candida albicans SC5314 chromosome features collected from Candida Genome Database 12-Jun 2018
• primary key: feature_name
• URL: http://www.candidagenome.org/download/chromosomal_feature_files/C_albicans_SC5314/C_albicans_SC5314_A22_current_chromosomal_feature.tab
• tab separated table with 13,281 rows

    Column:
    feature_name             <chr> "C1_00010W_A", "C1_00010W_B", "C1_00020C_A", ...
    gene_name                <chr> NA, NA, NA, NA, NA, NA, "CTA2", "CTA2", NA,  ...
    aliases                  <chr> "orf19.6115|C1_00010W_B|C1_00010W|orf19.1353 ...
    feature_type             <chr> "ORF|Dubious", "ORF", "ORF|Uncharacterized", ...
    chromosome               <chr> "Ca22chr1A_C_albicans_SC5314", "Ca22chr1B_C_ ...
    start_coordinate         <dbl> 4059, 4059, 4720, 4720, 8908, 8908, 10718, 1 ...
    stop_coordinate          <dbl> 4397, 4397, 4409, 4409, 8597, 8597, 11485, 1 ...
    strand                   <chr> "W", "W", "C", "C", "C", "C", "W", "W", "C", ...
    primary_cgd_id           <chr> "CAL0000182519", "CAL0000183273", "CAL000018 ...
    secondary_cgd_id         <chr> NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, "CAL ...
    description              <chr> "Dubious open reading frame", "Dubious open  ...
    creation_date            <date> 2014-06-24, 2014-06-24, 2014-06-24, 2014-06 ...
    sequence_coordinate_date <date> 2014-06-24, 2014-06-24, 2014-06-24, 2014-06 ...
    gene_name_date           <date> NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, ...
    gene_name_is_standard    <lgl> FALSE, FALSE, FALSE, FALSE, FALSE, FALSE, FA ...
    sac_ortholog             <chr> NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, "TUP ...
    feature_class            <chr> "ORF", "ORF", "ORF", "ORF", "ORF", "ORF", "O ...
    feature_status           <chr> "Dubious", NA, "Uncharacterized", NA, "Uncha ...
    is_alternatively_spliced <lgl> FALSE, FALSE, FALSE, FALSE, FALSE, FALSE, FA ...
    is_transposable_element  <lgl> FALSE, FALSE, FALSE, FALSE, FALSE, FALSE, FA ...
    rna_type                 <lgl> NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA,  ...
    is_blocked_reading_frame <lgl> FALSE, FALSE, FALSE, FALSE, FALSE, FALSE, FA ...

genes.tsv

• Curated set of 6226 genes use in this study
• primary key: feature_name
• foreign keys:
  • feature_name -> chromosome_features.feature_name
• tab separated table with 6,226 row

    Column:
    feature_name <chr> "C3_03580C_A", "C2_05660W_A", "C7_02860C_A", "C3_05180W_ ...

expression_runs.tsv

• Curated set of RNA-seq runs used in this study
• Collected from NCBI SRA
• primary key: run_accession
• tab separated table with 853 rows

    Column:
    submission_accession          <chr> "ERA237292", "ERA237292", "ERA237292",  ...
    submission_lab                <chr> "ArrayExpress", "ArrayExpress", "ArrayE ...
    updated_date                  <date> 2016-01-11, 2016-01-11, 2016-01-11, 20 ...
    sradb_updated                 <dttm> 2018-05-24 18:09:52, 2018-05-24 18:09: ...
    study_accession               <chr> "ERP003535", "ERP003535", "ERP003535",  ...
    study_alias                   <chr> "E-MTAB-1720", "E-MTAB-1720", "E-MTAB-1 ...
    study_name                    <chr> "E-MTAB-1720", "E-MTAB-1720", "E-MTAB-1 ...
    study_title                   <chr> "Initial stress responses of Candida al ...
    study_type                    <chr> "Transcriptome Analysis", "Transcriptom ...
    study_abstract                <chr> "A study was carried out to characteris ...
    center_project_name           <chr> "Initial stress responses of Candida al ...
    study_description             <chr> "A study was carried out to characteris ...
    study_attribute               <chr> "ArrayExpress: E-MTAB-1720", "ArrayExpr ...
    description                   <chr> "Protocols: Candida albicans (strain CA ...
    design_description            <chr> "Initial stress responses of Candida al ...
    sample_accession              <chr> "ERS323180", "ERS323177", "ERS323173",  ...
    sample_alias                  <chr> "E-MTAB-1720:NS B", "E-MTAB-1720:XS+NS  ...
    sample_name                   <chr> "E-MTAB-1720:NS B", "E-MTAB-1720:XS+NS  ...
    sample_attribute              <chr> "organism: Candida albicans || genotype ...
    taxon_id                      <dbl> 5476, 5476, 5476, 5476, 5476, 5476, 547 ...
    background_strain             <chr> "CAI4", "CAI4", "CAI4", "CAI4", "CAI4", ...
    platform                      <chr> "ILLUMINA", "ILLUMINA", "ILLUMINA", "IL ...
    platform_parameters           <chr> "INSTRUMENT_MODEL: Illumina HiSeq 2000" ...
    instrument_model              <chr> "Illumina HiSeq 2000", "Illumina HiSeq  ...
    library_name                  <chr> "NS B", "XS+NS D", "NS D", "XS+NS D", " ...
    library_strategy              <chr> "RNA-Seq", "RNA-Seq", "RNA-Seq", "RNA-S ...
    library_source                <chr> "TRANSCRIPTOMIC", "TRANSCRIPTOMIC", "TR ...
    library_selection             <chr> "cDNA", "cDNA", "cDNA", "cDNA", "cDNA", ...
    library_layout                <chr> "SINGLE -", "SINGLE -", "SINGLE -", "SI ...
    library_construction_protocol <chr> "Candida albicans (strain CAI4-CIp10) w ...
    is_paired                     <lgl> FALSE, FALSE, FALSE, FALSE, FALSE, FALS ...
    read_spec                     <chr> "READ_INDEX: 0; READ_CLASS: Application ...
    experiment_accession          <chr> "ERX283431", "ERX283301", "ERX283317",  ...
    experiment_alias              <chr> "E-MTAB-1720:120314_0166_D0814ACXX_3_SA ...
    experiment_name               <chr> "E-MTAB-1720:120314_0166_D0814ACXX_3_SA ...
    experiment_title              <chr> "Illumina HiSeq 2000 sequencing; Initia ...
    experiment_attribute          <chr> "Experimental Factor: compound_1: DPTA  ...
    run_accession                 <chr> "ERR310125", "ERR310018", "ERR309994",  ...
    run_alias                     <chr> "E-MTAB-1720:120314_0166_D0814ACXX_3_SA ...
    run_center                    <chr> "The GenePool, University of Edinburgh" ...
    spots                         <dbl> 1879764, 6330342, 5750605, 7088156, 649 ...
    bases                         <dbl> 95867964, 322847442, 293280855, 3614959 ...
    sra_fname                     <chr> "/nfs/ex7/work/momeara/ca_coexp/sra_806 ...
    year_collected                <dbl> 2018, 2018, 2018, 2018, 2018, 2018, 201 ...

estimated_expression.tsv

• gene by RNA-seq run expression levels
• primary key: gene_id, run_accession
• foreign keys:
  • gene_id -> genes.feature_name
  • run_accession -> expression_runs.run_accession
• The FPKM column represents the per-gene, per-run expression level
• tab separated table with 8,710,174 rows

    Column:
    gene_id          <chr> "C1_00010W_A", "C1_00020C_A", "C1_00030C_A", "C1_000 ...
    transcript_ids   <chr> "C1_00010W_A", "C1_00020C_A", "C1_00030C_A", "C1_000 ...
    length           <dbl> 339, 312, 312, 768, 348, 1539, 1089, 852, 522, 729,  ...
    effective_length <dbl> 290, 263, 263, 719, 299, 1490, 1040, 803, 473, 680,  ...
    expected_count   <dbl> 24.00, 2149.00, 355.01, 3219.94, 56.00, 8003.00, 696 ...
    TPM              <dbl> 3.38, 333.77, 55.14, 182.93, 7.65, 219.40, 273.72, 4 ...
    FPKM             <dbl> 4.36, 430.27, 71.08, 235.82, 9.86, 282.83, 352.86, 5 ...
    run_accession    <chr> "ERR1143627", "ERR1143627", "ERR1143627", "ERR114362 ...
    study_accession  <chr> "ERP013259", "ERP013259", "ERP013259", "ERP013259",  ...
    is_paired        <lgl> FALSE, FALSE, FALSE, FALSE, FALSE, FALSE, FALSE, FAL ...

CalCEN_network.tsv

• Co-expression network
• primary key: feature_name_1, feature_name_2
• foreign keys:
  • feature_name_1 -> genes.feature_name
  • feature_name_2 -> genes.feature_name
• score represents the scaled rank of the association between genes among all gene pairs.
• score >= .99 is the default threshold for a significant association
• tab separated table with 38,763,076 rows

    Column:
    feature_name_1 <chr> "C3_03580C_A", "C2_05660W_A", "C7_02860C_A", "C3_05180 ...
    feature_name_2 <chr> "C3_03580C_A", "C3_03580C_A", "C3_03580C_A", "C3_03580 ...
    score          <dbl> 1.00000000, 0.75060056, 0.40875062, 0.68047576, 0.3594 ...

blastp_network.tsv

• blastp sequence similarity network
• primary key: feature_name_1, feature_name_2
• foreign keys:
  • feature_name_1 -> genes.feature_name
  • feature_name_2 -> genes.feature_name
• score representes the scaled rank of the blastp Z-score among all significant gene pair associations (i.e. missing -> score = 0).
• tab separated table with 112,129 rows

    Column:
    feature_name_1 <chr> "C3_03580C_A", "C1_08890C_A", "CR_06460W_A", "C3_03600 ...
    feature_name_2 <chr> "C3_03580C_A", "C3_03580C_A", "C3_03580C_A", "C3_03580 ...
    score          <dbl> 0.95015957, 0.18948743, 0.27596712, 0.89713733, 0.0849 ...

sac_gene.tsv

• genetic associations between orthologous Sac genes Network
• primary key: feature_name_1, feature_name_2
• foreign keys:
  • feature_name_1 -> genes.feature_name
  • feature_name_2 -> genes.feature_name
• score represents the scaled rank of the the spearman correlation between between binary genetic association collected from BioGRID between orthologous genes from sac (higher is more siginficant)
• tab separated table with 38,763,076 rows

    Column:
    feature_name_1 <chr> "C3_03580C_A", "C2_05660W_A", "C7_02860C_A", "C3_05180 ...
    feature_name_2 <chr> "C3_03580C_A", "C3_03580C_A", "C3_03580C_A", "C3_03580 ...
    score          <dbl> 1.00000000, 0.61167254, 0.23926432, 0.40917646, 0.6116 ...

sac_gene.tsv

• physical protein-protein interaction between orthologous Sac genes Network
• primary key: feature_name_1, feature_name_2
• foreign keys:
  • feature_name_1 -> genes.feature_name
  • feature_name_2 -> genes.feature_name
• score represents the scaled rank of the the extended binary network between binary genetic association collected from BioGRID between orthologous genes from sac (higher is more siginficant).
• tab separated table with 14,671,296 rows and columns

     Column:
     feature_name_1 <chr> "C3_03580C_A", "C2_05660W_A", "C7_02860C_A", "C3_05180 ...
     feature_name_2 <chr> "C3_03580C_A", "C2_05660W_A", "C7_02860C_A", "C7_02860 ...
     score          <dbl> 1.0000000, 1.0000000, 1.0000000, 0.5000000, 0.5000000, ...

yeast_net_network.tsv

• YeastNet between orthologous Sac genes network
• primary key: feature_name_1, feature_name_2
• foreign keys:
  • feature_name_1 -> genes.feature_name
  • feature_name_2 -> genes.feature_name
• score is taken directly from the YeastNet network
• tab separated table with 425,792 rows

    Column:
    feature_name_1 <chr> "C1_12750C_A", "C5_05140W_A", "CR_07620W_A", "C7_04040 ...
    feature_name_2 <chr> "C7_02860C_A", "C7_02860C_A", "C7_02860C_A", "C7_02860 ...
    score          <dbl> 2.300967, 2.415099, 2.300967, 2.309640, 2.337247, 2.22 ...

go_annotations.tsv

• GO annotations from Candida Genome Database collected 12-Jun 2018
• URL: http://www.candidagenome.org/download/go/gene_association.cgd.gz
• primary key: feature_name, go_id
• foreign keys:
  • feature_name -> genes.feature_name
• values exclude NOT annotations and are propagated up the ontological hierarchy
• tab separated table with 29,159 rows

    Column:
    feature_name <chr> "C1_00100C_A", "C1_00640C_A", "C1_02660C_A", "C1_03540C_ ...
    go_id        <chr> "GO.0000002", "GO.0000002", "GO.0000002", "GO.0000002",  ...

gba_summary.tsv

• Summary of guilt-by-association gene-function prediction
• primary key: anno_id, network_id
• anno_id in [all, MF, BB, CC]
• network_id is a set of networks ids separated by '|'
• auroc_mean is the mean area under the ROC curve summarized over 10-fold cross validation and auroc_std is the standard deviation
• degree_null_auroc_mean is the degree null predictor scores and degree_null_auroc_std is the standard deviation
• tab separated table with 125 rows

    Column:
    anno_id                <chr> "all", "all", "all", "all", "all", "all", "all ...
    network_id             <chr> "CalCEN", "BlastP", "SacPhys", "SacGene", "Yea ...
    auroc_mean             <dbl> 0.7522911, 0.6880802, 0.7713754, 0.7525273, 0. ...
    auroc_std              <dbl> 0.08311475, 0.11720483, 0.17135738, 0.12416886 ...
    degree_null_auroc_mean <dbl> 0.5111914, 0.5473948, 0.5996210, 0.5926223, 0. ...
    degree_null_auroc_std  <dbl> 0.1069059, 0.1418470, 0.1340942, 0.1316009, 0. ...