Contents

Introduction

Motivation: New technologies have made possible to identify marker gene signatures. However, gene expression-based signatures present some limitations because they do not consider metabolic role of the genes and are affected by genetic heterogeneity across patient cohorts. Considering the activity of entire pathways rather than the expression levels of individual genes can be a way to exceed these limits (Cancer Genome Atlas Research Network and others 2012). This tool StarBioTrek presents some methodologies to measure pathway activity and cross-talk among pathways integrating also the information of network and TCGA data. New measures are under development.

Installation

To install use the code below.

if (!requireNamespace("BiocManager", quietly=TRUE))
    install.packages("BiocManager")
BiocManager::install("StarBioTrek")

Get data: Get pathway and network data

SELECT_path_species: Select the pathway database and species of interest

The user can select the pathway database and species of interest using some functions implemented in graphite (Sales G, et al. 2012)

library(graphite)
sel<-pathwayDatabases()

Table 1: List of patwhay databases and species
species database
athaliana kegg
athaliana pathbank
athaliana wikipathways
btaurus kegg
btaurus pathbank
btaurus reactome
btaurus wikipathways
celegans kegg
celegans pathbank
celegans reactome
celegans wikipathways
cfamiliaris kegg
cfamiliaris reactome
cfamiliaris wikipathways
dmelanogaster kegg
dmelanogaster pathbank
dmelanogaster reactome
dmelanogaster wikipathways
drerio kegg
drerio reactome
drerio wikipathways
ecoli kegg
ecoli pathbank
ecoli wikipathways
ggallus kegg
ggallus reactome
ggallus wikipathways
hsapiens kegg
hsapiens panther
hsapiens pathbank
hsapiens pharmgkb
hsapiens reactome
hsapiens smpdb
hsapiens wikipathways
mmusculus kegg
mmusculus pathbank
mmusculus reactome
mmusculus wikipathways
rnorvegicus kegg
rnorvegicus pathbank
rnorvegicus reactome
rnorvegicus wikipathways
scerevisiae kegg
scerevisiae pathbank
scerevisiae reactome
scerevisiae wikipathways
sscrofa kegg
sscrofa reactome
sscrofa wikipathways
xlaevis kegg

GetData: Searching pathway data for download

The user can easily search pathways data and their genes using the GetData function. It can download pathways from several databases and species using the following parameters:

species="hsapiens"
pathwaydb="kegg"
path<-GetData(species,pathwaydb)
## [1] "Querying.............  Glycolysis / Gluconeogenesis   1 of 326 pathways"
## [1] "Querying.............  Citrate cycle (TCA cycle)   2 of 326 pathways"
## [1] "Querying.............  Pentose phosphate pathway   3 of 326 pathways"
## [1] "Querying.............  Pentose and glucuronate interconversions   4 of 326 pathways"
## [1] "Querying.............  Fructose and mannose metabolism   5 of 326 pathways"
## [1] "Querying.............  Galactose metabolism   6 of 326 pathways"
## [1] "Querying.............  Ascorbate and aldarate metabolism   7 of 326 pathways"
## [1] "Querying.............  Fatty acid biosynthesis   8 of 326 pathways"
## [1] "Querying.............  Fatty acid elongation   9 of 326 pathways"
## [1] "Querying.............  Fatty acid degradation   10 of 326 pathways"
## [1] "Querying.............  Steroid biosynthesis   11 of 326 pathways"
## [1] "Querying.............  Primary bile acid biosynthesis   12 of 326 pathways"
## [1] "Querying.............  Ubiquinone and other terpenoid-quinone biosynthesis   13 of 326 pathways"
## [1] "Querying.............  Steroid hormone biosynthesis   14 of 326 pathways"
## [1] "Querying.............  Oxidative phosphorylation   15 of 326 pathways"
## [1] "Querying.............  Arginine biosynthesis   16 of 326 pathways"
## [1] "Querying.............  Purine metabolism   17 of 326 pathways"
## [1] "Querying.............  Caffeine metabolism   18 of 326 pathways"
## [1] "Querying.............  Pyrimidine metabolism   19 of 326 pathways"
## [1] "Querying.............  Alanine, aspartate and glutamate metabolism   20 of 326 pathways"
## [1] "Querying.............  Glycine, serine and threonine metabolism   21 of 326 pathways"
## [1] "Querying.............  Cysteine and methionine metabolism   22 of 326 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine degradation   23 of 326 pathways"
## [1] "Querying.............  Lysine degradation   24 of 326 pathways"
## [1] "Querying.............  Arginine and proline metabolism   25 of 326 pathways"
## [1] "Querying.............  Histidine metabolism   26 of 326 pathways"
## [1] "Querying.............  Tyrosine metabolism   27 of 326 pathways"
## [1] "Querying.............  Phenylalanine metabolism   28 of 326 pathways"
## [1] "Querying.............  Tryptophan metabolism   29 of 326 pathways"
## [1] "Querying.............  Phenylalanine, tyrosine and tryptophan biosynthesis   30 of 326 pathways"
## [1] "Querying.............  beta-Alanine metabolism   31 of 326 pathways"
## [1] "Querying.............  Taurine and hypotaurine metabolism   32 of 326 pathways"
## [1] "Querying.............  Phosphonate and phosphinate metabolism   33 of 326 pathways"
## [1] "Querying.............  Selenocompound metabolism   34 of 326 pathways"
## [1] "Querying.............  D-Amino acid metabolism   35 of 326 pathways"
## [1] "Querying.............  Glutathione metabolism   36 of 326 pathways"
## [1] "Querying.............  Starch and sucrose metabolism   37 of 326 pathways"
## [1] "Querying.............  N-Glycan biosynthesis   38 of 326 pathways"
## [1] "Querying.............  Mucin type O-glycan biosynthesis   39 of 326 pathways"
## [1] "Querying.............  Various types of N-glycan biosynthesis   40 of 326 pathways"
## [1] "Querying.............  Mannose type O-glycan biosynthesis   41 of 326 pathways"
## [1] "Querying.............  Amino sugar and nucleotide sugar metabolism   42 of 326 pathways"
## [1] "Querying.............  Glycosaminoglycan degradation   43 of 326 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate   44 of 326 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - heparan sulfate / heparin   45 of 326 pathways"
## [1] "Querying.............  Glycerolipid metabolism   46 of 326 pathways"
## [1] "Querying.............  Inositol phosphate metabolism   47 of 326 pathways"
## [1] "Querying.............  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis   48 of 326 pathways"
## [1] "Querying.............  Glycerophospholipid metabolism   49 of 326 pathways"
## [1] "Querying.............  Ether lipid metabolism   50 of 326 pathways"
## [1] "Querying.............  Arachidonic acid metabolism   51 of 326 pathways"
## [1] "Querying.............  Linoleic acid metabolism   52 of 326 pathways"
## [1] "Querying.............  alpha-Linolenic acid metabolism   53 of 326 pathways"
## [1] "Querying.............  Sphingolipid metabolism   54 of 326 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - lacto and neolacto series   55 of 326 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - globo and isoglobo series   56 of 326 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - ganglio series   57 of 326 pathways"
## [1] "Querying.............  Pyruvate metabolism   58 of 326 pathways"
## [1] "Querying.............  Glyoxylate and dicarboxylate metabolism   59 of 326 pathways"
## [1] "Querying.............  Propanoate metabolism   60 of 326 pathways"
## [1] "Querying.............  Butanoate metabolism   61 of 326 pathways"
## [1] "Querying.............  One carbon pool by folate   62 of 326 pathways"
## [1] "Querying.............  Thiamine metabolism   63 of 326 pathways"
## [1] "Querying.............  Riboflavin metabolism   64 of 326 pathways"
## [1] "Querying.............  Vitamin B6 metabolism   65 of 326 pathways"
## [1] "Querying.............  Nicotinate and nicotinamide metabolism   66 of 326 pathways"
## [1] "Querying.............  Pantothenate and CoA biosynthesis   67 of 326 pathways"
## [1] "Querying.............  Biotin metabolism   68 of 326 pathways"
## [1] "Querying.............  Lipoic acid metabolism   69 of 326 pathways"
## [1] "Querying.............  Folate biosynthesis   70 of 326 pathways"
## [1] "Querying.............  Retinol metabolism   71 of 326 pathways"
## [1] "Querying.............  Porphyrin metabolism   72 of 326 pathways"
## [1] "Querying.............  Terpenoid backbone biosynthesis   73 of 326 pathways"
## [1] "Querying.............  Nitrogen metabolism   74 of 326 pathways"
## [1] "Querying.............  Sulfur metabolism   75 of 326 pathways"
## [1] "Querying.............  Aminoacyl-tRNA biosynthesis   76 of 326 pathways"
## [1] "Querying.............  Metabolism of xenobiotics by cytochrome P450   77 of 326 pathways"
## [1] "Querying.............  Drug metabolism - cytochrome P450   78 of 326 pathways"
## [1] "Querying.............  Drug metabolism - other enzymes   79 of 326 pathways"
## [1] "Querying.............  Biosynthesis of unsaturated fatty acids   80 of 326 pathways"
## [1] "Querying.............  Metabolic pathways   81 of 326 pathways"
## [1] "Querying.............  Carbon metabolism   82 of 326 pathways"
## [1] "Querying.............  2-Oxocarboxylic acid metabolism   83 of 326 pathways"
## [1] "Querying.............  Fatty acid metabolism   84 of 326 pathways"
## [1] "Querying.............  Biosynthesis of amino acids   85 of 326 pathways"
## [1] "Querying.............  Nucleotide metabolism   86 of 326 pathways"
## [1] "Querying.............  Biosynthesis of cofactors   87 of 326 pathways"
## [1] "Querying.............  Biosynthesis of nucleotide sugars   88 of 326 pathways"
## [1] "Querying.............  EGFR tyrosine kinase inhibitor resistance   89 of 326 pathways"
## [1] "Querying.............  Endocrine resistance   90 of 326 pathways"
## [1] "Querying.............  Antifolate resistance   91 of 326 pathways"
## [1] "Querying.............  Platinum drug resistance   92 of 326 pathways"
## [1] "Querying.............  mRNA surveillance pathway   93 of 326 pathways"
## [1] "Querying.............  RNA degradation   94 of 326 pathways"
## [1] "Querying.............  Viral life cycle - HIV-1   95 of 326 pathways"
## [1] "Querying.............  PPAR signaling pathway   96 of 326 pathways"
## [1] "Querying.............  Homologous recombination   97 of 326 pathways"
## [1] "Querying.............  Fanconi anemia pathway   98 of 326 pathways"
## [1] "Querying.............  MAPK signaling pathway   99 of 326 pathways"
## [1] "Querying.............  ErbB signaling pathway   100 of 326 pathways"
## [1] "Querying.............  Ras signaling pathway   101 of 326 pathways"
## [1] "Querying.............  Rap1 signaling pathway   102 of 326 pathways"
## [1] "Querying.............  Calcium signaling pathway   103 of 326 pathways"
## [1] "Querying.............  cGMP-PKG signaling pathway   104 of 326 pathways"
## [1] "Querying.............  cAMP signaling pathway   105 of 326 pathways"
## [1] "Querying.............  Cytokine-cytokine receptor interaction   106 of 326 pathways"
## [1] "Querying.............  Viral protein interaction with cytokine and cytokine receptor   107 of 326 pathways"
## [1] "Querying.............  Chemokine signaling pathway   108 of 326 pathways"
## [1] "Querying.............  NF-kappa B signaling pathway   109 of 326 pathways"
## [1] "Querying.............  HIF-1 signaling pathway   110 of 326 pathways"
## [1] "Querying.............  FoxO signaling pathway   111 of 326 pathways"
## [1] "Querying.............  Phosphatidylinositol signaling system   112 of 326 pathways"
## [1] "Querying.............  Sphingolipid signaling pathway   113 of 326 pathways"
## [1] "Querying.............  Phospholipase D signaling pathway   114 of 326 pathways"
## [1] "Querying.............  Neuroactive ligand-receptor interaction   115 of 326 pathways"
## [1] "Querying.............  Cell cycle   116 of 326 pathways"
## [1] "Querying.............  Oocyte meiosis   117 of 326 pathways"
## [1] "Querying.............  p53 signaling pathway   118 of 326 pathways"
## [1] "Querying.............  Sulfur relay system   119 of 326 pathways"
## [1] "Querying.............  SNARE interactions in vesicular transport   120 of 326 pathways"
## [1] "Querying.............  Autophagy - other   121 of 326 pathways"
## [1] "Querying.............  Mitophagy - animal   122 of 326 pathways"
## [1] "Querying.............  Autophagy - animal   123 of 326 pathways"
## [1] "Querying.............  Protein processing in endoplasmic reticulum   124 of 326 pathways"
## [1] "Querying.............  Endocytosis   125 of 326 pathways"
## [1] "Querying.............  Phagosome   126 of 326 pathways"
## [1] "Querying.............  Peroxisome   127 of 326 pathways"
## [1] "Querying.............  Efferocytosis   128 of 326 pathways"
## [1] "Querying.............  mTOR signaling pathway   129 of 326 pathways"
## [1] "Querying.............  PI3K-Akt signaling pathway   130 of 326 pathways"
## [1] "Querying.............  AMPK signaling pathway   131 of 326 pathways"
## [1] "Querying.............  Apoptosis   132 of 326 pathways"
## [1] "Querying.............  Longevity regulating pathway   133 of 326 pathways"
## [1] "Querying.............  Longevity regulating pathway - multiple species   134 of 326 pathways"
## [1] "Querying.............  Apoptosis - multiple species   135 of 326 pathways"
## [1] "Querying.............  Ferroptosis   136 of 326 pathways"
## [1] "Querying.............  Necroptosis   137 of 326 pathways"
## [1] "Querying.............  Cellular senescence   138 of 326 pathways"
## [1] "Querying.............  Cardiac muscle contraction   139 of 326 pathways"
## [1] "Querying.............  Adrenergic signaling in cardiomyocytes   140 of 326 pathways"
## [1] "Querying.............  Vascular smooth muscle contraction   141 of 326 pathways"
## [1] "Querying.............  Wnt signaling pathway   142 of 326 pathways"
## [1] "Querying.............  Notch signaling pathway   143 of 326 pathways"
## [1] "Querying.............  Hedgehog signaling pathway   144 of 326 pathways"
## [1] "Querying.............  TGF-beta signaling pathway   145 of 326 pathways"
## [1] "Querying.............  Axon guidance   146 of 326 pathways"
## [1] "Querying.............  VEGF signaling pathway   147 of 326 pathways"
## [1] "Querying.............  Apelin signaling pathway   148 of 326 pathways"
## [1] "Querying.............  Osteoclast differentiation   149 of 326 pathways"
## [1] "Querying.............  Hippo signaling pathway   150 of 326 pathways"
## [1] "Querying.............  Hippo signaling pathway - multiple species   151 of 326 pathways"
## [1] "Querying.............  Focal adhesion   152 of 326 pathways"
## [1] "Querying.............  ECM-receptor interaction   153 of 326 pathways"
## [1] "Querying.............  Cell adhesion molecules   154 of 326 pathways"
## [1] "Querying.............  Adherens junction   155 of 326 pathways"
## [1] "Querying.............  Tight junction   156 of 326 pathways"
## [1] "Querying.............  Gap junction   157 of 326 pathways"
## [1] "Querying.............  Signaling pathways regulating pluripotency of stem cells   158 of 326 pathways"
## [1] "Querying.............  Complement and coagulation cascades   159 of 326 pathways"
## [1] "Querying.............  Platelet activation   160 of 326 pathways"
## [1] "Querying.............  Antigen processing and presentation   161 of 326 pathways"
## [1] "Querying.............  Neutrophil extracellular trap formation   162 of 326 pathways"
## [1] "Querying.............  Renin-angiotensin system   163 of 326 pathways"
## [1] "Querying.............  Toll-like receptor signaling pathway   164 of 326 pathways"
## [1] "Querying.............  NOD-like receptor signaling pathway   165 of 326 pathways"
## [1] "Querying.............  RIG-I-like receptor signaling pathway   166 of 326 pathways"
## [1] "Querying.............  Cytosolic DNA-sensing pathway   167 of 326 pathways"
## [1] "Querying.............  C-type lectin receptor signaling pathway   168 of 326 pathways"
## [1] "Querying.............  JAK-STAT signaling pathway   169 of 326 pathways"
## [1] "Querying.............  Natural killer cell mediated cytotoxicity   170 of 326 pathways"
## [1] "Querying.............  IL-17 signaling pathway   171 of 326 pathways"
## [1] "Querying.............  Th1 and Th2 cell differentiation   172 of 326 pathways"
## [1] "Querying.............  Th17 cell differentiation   173 of 326 pathways"
## [1] "Querying.............  T cell receptor signaling pathway   174 of 326 pathways"
## [1] "Querying.............  B cell receptor signaling pathway   175 of 326 pathways"
## [1] "Querying.............  Fc epsilon RI signaling pathway   176 of 326 pathways"
## [1] "Querying.............  Fc gamma R-mediated phagocytosis   177 of 326 pathways"
## [1] "Querying.............  TNF signaling pathway   178 of 326 pathways"
## [1] "Querying.............  Leukocyte transendothelial migration   179 of 326 pathways"
## [1] "Querying.............  Intestinal immune network for IgA production   180 of 326 pathways"
## [1] "Querying.............  Circadian rhythm   181 of 326 pathways"
## [1] "Querying.............  Circadian entrainment   182 of 326 pathways"
## [1] "Querying.............  Thermogenesis   183 of 326 pathways"
## [1] "Querying.............  Long-term potentiation   184 of 326 pathways"
## [1] "Querying.............  Synaptic vesicle cycle   185 of 326 pathways"
## [1] "Querying.............  Neurotrophin signaling pathway   186 of 326 pathways"
## [1] "Querying.............  Retrograde endocannabinoid signaling   187 of 326 pathways"
## [1] "Querying.............  Glutamatergic synapse   188 of 326 pathways"
## [1] "Querying.............  Cholinergic synapse   189 of 326 pathways"
## [1] "Querying.............  Serotonergic synapse   190 of 326 pathways"
## [1] "Querying.............  GABAergic synapse   191 of 326 pathways"
## [1] "Querying.............  Dopaminergic synapse   192 of 326 pathways"
## [1] "Querying.............  Long-term depression   193 of 326 pathways"
## [1] "Querying.............  Olfactory transduction   194 of 326 pathways"
## [1] "Querying.............  Taste transduction   195 of 326 pathways"
## [1] "Querying.............  Phototransduction   196 of 326 pathways"
## [1] "Querying.............  Inflammatory mediator regulation of TRP channels   197 of 326 pathways"
## [1] "Querying.............  Regulation of actin cytoskeleton   198 of 326 pathways"
## [1] "Querying.............  Insulin signaling pathway   199 of 326 pathways"
## [1] "Querying.............  Insulin secretion   200 of 326 pathways"
## [1] "Querying.............  GnRH signaling pathway   201 of 326 pathways"
## [1] "Querying.............  Ovarian steroidogenesis   202 of 326 pathways"
## [1] "Querying.............  Progesterone-mediated oocyte maturation   203 of 326 pathways"
## [1] "Querying.............  Estrogen signaling pathway   204 of 326 pathways"
## [1] "Querying.............  Melanogenesis   205 of 326 pathways"
## [1] "Querying.............  Prolactin signaling pathway   206 of 326 pathways"
## [1] "Querying.............  Thyroid hormone synthesis   207 of 326 pathways"
## [1] "Querying.............  Thyroid hormone signaling pathway   208 of 326 pathways"
## [1] "Querying.............  Adipocytokine signaling pathway   209 of 326 pathways"
## [1] "Querying.............  Oxytocin signaling pathway   210 of 326 pathways"
## [1] "Querying.............  Glucagon signaling pathway   211 of 326 pathways"
## [1] "Querying.............  Regulation of lipolysis in adipocytes   212 of 326 pathways"
## [1] "Querying.............  Renin secretion   213 of 326 pathways"
## [1] "Querying.............  Aldosterone synthesis and secretion   214 of 326 pathways"
## [1] "Querying.............  Relaxin signaling pathway   215 of 326 pathways"
## [1] "Querying.............  Cortisol synthesis and secretion   216 of 326 pathways"
## [1] "Querying.............  Parathyroid hormone synthesis, secretion and action   217 of 326 pathways"
## [1] "Querying.............  GnRH secretion   218 of 326 pathways"
## [1] "Querying.............  Type II diabetes mellitus   219 of 326 pathways"
## [1] "Querying.............  Insulin resistance   220 of 326 pathways"
## [1] "Querying.............  Non-alcoholic fatty liver disease   221 of 326 pathways"
## [1] "Querying.............  AGE-RAGE signaling pathway in diabetic complications   222 of 326 pathways"
## [1] "Querying.............  Cushing syndrome   223 of 326 pathways"
## [1] "Querying.............  Growth hormone synthesis, secretion and action   224 of 326 pathways"
## [1] "Querying.............  Alcoholic liver disease   225 of 326 pathways"
## [1] "Querying.............  Type I diabetes mellitus   226 of 326 pathways"
## [1] "Querying.............  Maturity onset diabetes of the young   227 of 326 pathways"
## [1] "Querying.............  Aldosterone-regulated sodium reabsorption   228 of 326 pathways"
## [1] "Querying.............  Endocrine and other factor-regulated calcium reabsorption   229 of 326 pathways"
## [1] "Querying.............  Vasopressin-regulated water reabsorption   230 of 326 pathways"
## [1] "Querying.............  Proximal tubule bicarbonate reclamation   231 of 326 pathways"
## [1] "Querying.............  Salivary secretion   232 of 326 pathways"
## [1] "Querying.............  Gastric acid secretion   233 of 326 pathways"
## [1] "Querying.............  Pancreatic secretion   234 of 326 pathways"
## [1] "Querying.............  Carbohydrate digestion and absorption   235 of 326 pathways"
## [1] "Querying.............  Fat digestion and absorption   236 of 326 pathways"
## [1] "Querying.............  Bile secretion   237 of 326 pathways"
## [1] "Querying.............  Vitamin digestion and absorption   238 of 326 pathways"
## [1] "Querying.............  Mineral absorption   239 of 326 pathways"
## [1] "Querying.............  Cholesterol metabolism   240 of 326 pathways"
## [1] "Querying.............  Alzheimer disease   241 of 326 pathways"
## [1] "Querying.............  Parkinson disease   242 of 326 pathways"
## [1] "Querying.............  Amyotrophic lateral sclerosis   243 of 326 pathways"
## [1] "Querying.............  Huntington disease   244 of 326 pathways"
## [1] "Querying.............  Spinocerebellar ataxia   245 of 326 pathways"
## [1] "Querying.............  Prion disease   246 of 326 pathways"
## [1] "Querying.............  Pathways of neurodegeneration - multiple diseases   247 of 326 pathways"
## [1] "Querying.............  Cocaine addiction   248 of 326 pathways"
## [1] "Querying.............  Amphetamine addiction   249 of 326 pathways"
## [1] "Querying.............  Morphine addiction   250 of 326 pathways"
## [1] "Querying.............  Alcoholism   251 of 326 pathways"
## [1] "Querying.............  Bacterial invasion of epithelial cells   252 of 326 pathways"
## [1] "Querying.............  Vibrio cholerae infection   253 of 326 pathways"
## [1] "Querying.............  Epithelial cell signaling in Helicobacter pylori infection   254 of 326 pathways"
## [1] "Querying.............  Pathogenic Escherichia coli infection   255 of 326 pathways"
## [1] "Querying.............  Shigellosis   256 of 326 pathways"
## [1] "Querying.............  Salmonella infection   257 of 326 pathways"
## [1] "Querying.............  Pertussis   258 of 326 pathways"
## [1] "Querying.............  Legionellosis   259 of 326 pathways"
## [1] "Querying.............  Yersinia infection   260 of 326 pathways"
## [1] "Querying.............  Leishmaniasis   261 of 326 pathways"
## [1] "Querying.............  Chagas disease   262 of 326 pathways"
## [1] "Querying.............  African trypanosomiasis   263 of 326 pathways"
## [1] "Querying.............  Malaria   264 of 326 pathways"
## [1] "Querying.............  Toxoplasmosis   265 of 326 pathways"
## [1] "Querying.............  Amoebiasis   266 of 326 pathways"
## [1] "Querying.............  Staphylococcus aureus infection   267 of 326 pathways"
## [1] "Querying.............  Tuberculosis   268 of 326 pathways"
## [1] "Querying.............  Hepatitis C   269 of 326 pathways"
## [1] "Querying.............  Hepatitis B   270 of 326 pathways"
## [1] "Querying.............  Measles   271 of 326 pathways"
## [1] "Querying.............  Human cytomegalovirus infection   272 of 326 pathways"
## [1] "Querying.............  Influenza A   273 of 326 pathways"
## [1] "Querying.............  Human papillomavirus infection   274 of 326 pathways"
## [1] "Querying.............  Human T-cell leukemia virus 1 infection   275 of 326 pathways"
## [1] "Querying.............  Kaposi sarcoma-associated herpesvirus infection   276 of 326 pathways"
## [1] "Querying.............  Herpes simplex virus 1 infection   277 of 326 pathways"
## [1] "Querying.............  Epstein-Barr virus infection   278 of 326 pathways"
## [1] "Querying.............  Human immunodeficiency virus 1 infection   279 of 326 pathways"
## [1] "Querying.............  Coronavirus disease - COVID-19   280 of 326 pathways"
## [1] "Querying.............  Pathways in cancer   281 of 326 pathways"
## [1] "Querying.............  Transcriptional misregulation in cancer   282 of 326 pathways"
## [1] "Querying.............  Viral carcinogenesis   283 of 326 pathways"
## [1] "Querying.............  Chemical carcinogenesis - DNA adducts   284 of 326 pathways"
## [1] "Querying.............  Proteoglycans in cancer   285 of 326 pathways"
## [1] "Querying.............  MicroRNAs in cancer   286 of 326 pathways"
## [1] "Querying.............  Chemical carcinogenesis - receptor activation   287 of 326 pathways"
## [1] "Querying.............  Chemical carcinogenesis - reactive oxygen species   288 of 326 pathways"
## [1] "Querying.............  Colorectal cancer   289 of 326 pathways"
## [1] "Querying.............  Renal cell carcinoma   290 of 326 pathways"
## [1] "Querying.............  Pancreatic cancer   291 of 326 pathways"
## [1] "Querying.............  Endometrial cancer   292 of 326 pathways"
## [1] "Querying.............  Glioma   293 of 326 pathways"
## [1] "Querying.............  Prostate cancer   294 of 326 pathways"
## [1] "Querying.............  Thyroid cancer   295 of 326 pathways"
## [1] "Querying.............  Basal cell carcinoma   296 of 326 pathways"
## [1] "Querying.............  Melanoma   297 of 326 pathways"
## [1] "Querying.............  Bladder cancer   298 of 326 pathways"
## [1] "Querying.............  Chronic myeloid leukemia   299 of 326 pathways"
## [1] "Querying.............  Acute myeloid leukemia   300 of 326 pathways"
## [1] "Querying.............  Small cell lung cancer   301 of 326 pathways"
## [1] "Querying.............  Non-small cell lung cancer   302 of 326 pathways"
## [1] "Querying.............  Breast cancer   303 of 326 pathways"
## [1] "Querying.............  Hepatocellular carcinoma   304 of 326 pathways"
## [1] "Querying.............  Gastric cancer   305 of 326 pathways"
## [1] "Querying.............  Central carbon metabolism in cancer   306 of 326 pathways"
## [1] "Querying.............  Choline metabolism in cancer   307 of 326 pathways"
## [1] "Querying.............  PD-L1 expression and PD-1 checkpoint pathway in cancer   308 of 326 pathways"
## [1] "Querying.............  Asthma   309 of 326 pathways"
## [1] "Querying.............  Autoimmune thyroid disease   310 of 326 pathways"
## [1] "Querying.............  Inflammatory bowel disease   311 of 326 pathways"
## [1] "Querying.............  Systemic lupus erythematosus   312 of 326 pathways"
## [1] "Querying.............  Rheumatoid arthritis   313 of 326 pathways"
## [1] "Querying.............  Allograft rejection   314 of 326 pathways"
## [1] "Querying.............  Graft-versus-host disease   315 of 326 pathways"
## [1] "Querying.............  Hypertrophic cardiomyopathy   316 of 326 pathways"
## [1] "Querying.............  Arrhythmogenic right ventricular cardiomyopathy   317 of 326 pathways"
## [1] "Querying.............  Dilated cardiomyopathy   318 of 326 pathways"
## [1] "Querying.............  Diabetic cardiomyopathy   319 of 326 pathways"
## [1] "Querying.............  Viral myocarditis   320 of 326 pathways"
## [1] "Querying.............  Lipid and atherosclerosis   321 of 326 pathways"
## [1] "Querying.............  Fluid shear stress and atherosclerosis   322 of 326 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine biosynthesis   323 of 326 pathways"
## [1] "Querying.............  Neomycin, kanamycin and gentamicin biosynthesis   324 of 326 pathways"
## [1] "Querying.............  Protein digestion and absorption   325 of 326 pathways"
## [1] "Querying.............  Nicotine addiction   326 of 326 pathways"

GetPathData: Get genes inside pathways

The user can identify the genes inside the pathways of interest

pathway_ALLGENE<-GetPathData(path_ALL=path[1:3])

GetPathNet: Get interacting genes inside pathways

GetPathNet generates a list of interacting genes for each pathway

pathway_net<-GetPathNet(path_ALL=path[1:3])

ConvertedIDgenes: Get genes inside pathways

The user can convert the gene ID into GeneSymbol

pathway<-ConvertedIDgenes(path_ALL=path[1:10])
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Glycolysis / Gluconeogenesis   1 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Citrate cycle (TCA cycle)   2 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Pentose phosphate pathway   3 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Pentose and glucuronate interconversions   4 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Fructose and mannose metabolism   5 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Galactose metabolism   6 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Ascorbate and aldarate metabolism   7 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Fatty acid biosynthesis   8 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Fatty acid elongation   9 of 10 pathways"
## [1] "Mapping Uniprot ID to Gene Symbol, using convertIdentifiers of graphite package..........  Fatty acid degradation   10 of 10 pathways"

getNETdata: Searching network data for download

You can easily search human network data from GeneMania using the getNETdata function (Warde-Farley D, et al. 2010). The network category can be filtered using the following parameters:

  • PHint Physical_interactions
  • COloc Co-localization
  • GENint Genetic_interactions
  • PATH Pathway
  • SHpd Shared_protein_domains

The species can be filtered using the following parameters: * Arabidopsis_thaliana * Caenorhabditis_elegans * Danio_rerio * Drosophila_melanogaster * Escherichia_coli * Homo_sapiens * Mus_musculus * Rattus_norvegicus * Saccharomyces_cerevisiae

For default the organism is homo sapiens. The example show the shared protein domain network for Saccharomyces_cerevisiae. For more information see SpidermiR package.

organismID="Saccharomyces_cerevisiae"
netw<-getNETdata(network="SHpd",organismID)
## [1] "Downloading: http://genemania.org/data/current/Saccharomyces_cerevisiae/Shared_protein_domains.INTERPRO.txt ... reference n. 1 of 2"
## [1] "Downloading: http://genemania.org/data/current/Saccharomyces_cerevisiae/Shared_protein_domains.PFAM.txt ... reference n. 2 of 2"
## [1] "Preprocessing of the network n. 1 of 2"
## [1] "Preprocessing of the network n. 2 of 2"

Integration data: Integration between pathway and network data

path_net: Network of interacting genes for each pathway according a network type (PHint,COloc,GENint,PATH,SHpd)

The function path_net creates a network of interacting genes (downloaded from GeneMania) for each pathway. Interacting genes are genes belonging to the same pathway and the interaction is given from network chosen by the user, according the paramenters of the function getNETdata. The output will be a network of genes belonging to the same pathway.

lista_net<-pathnet(genes.by.pathway=pathway[1:5],data=netw)
## [1] "Glycolysis / Gluconeogenesis"
## [1] "Citrate cycle (TCA cycle)"
## [1] "Pentose phosphate pathway"
## [1] "Pentose and glucuronate interconversions"
## [1] "Fructose and mannose metabolism"

list_path_net: List of interacting genes for each pathway (list of genes) according a network type (PHint,COloc,GENint,PATH,SHpd)

The function list_path_net creates a list of interacting genes for each pathway. Interacting genes are genes belonging to the same pathway and the interaction is given from network chosen by the user, according the paramenters of the function getNETdata. The output will be a list of genes belonging to the same pathway and those having an interaction in the network.

list_path<-listpathnet(lista_net=lista_net,pathway=pathway[1:5])
## [1] "List of genes interacting in the same pathway: Glycolysis / Gluconeogenesis"
## [1] "List of genes interacting in the same pathway: Citrate cycle (TCA cycle)"
## [1] "List of genes interacting in the same pathway: Pentose phosphate pathway"
## [1] "List of genes interacting in the same pathway: Pentose and glucuronate interconversions"
## [1] "List of genes interacting in the same pathway: Fructose and mannose metabolism"

Pathway summary indexes: Score for each pathway

GE_matrix: grouping gene expression profiles in pathways

Get human KEGG pathway data and a gene expression matrix in order to obtain a matrix with the gene expression levels grouped by pathways.

Starting from a matrix of gene expression (rows are genes and columns are samples, TCGA data) the function GE_matrix creates a profile of gene expression levels for each pathway given by the user:

list_path_gene<-GE_matrix(DataMatrix=tumo[,1:2],genes.by.pathway=pathway[1:10])
## [1] "Glycolysis / Gluconeogenesis"
## [1] "Citrate cycle (TCA cycle)"
## [1] "Pentose phosphate pathway"
## [1] "Pentose and glucuronate interconversions"
## [1] "Fructose and mannose metabolism"
## [1] "Galactose metabolism"
## [1] "Ascorbate and aldarate metabolism"
## [1] "Fatty acid biosynthesis"
## [1] "Fatty acid elongation"
## [1] "Fatty acid degradation"

GE_matrix_mean:

Get human KEGG pathway data and a gene expression matrix in order to obtain a matrix PXG (in the columns there are the pathways and in the rows there are genes) with the mean gene expression for only genes given containing in the pathways given in input by the user.

list_path_plot<-GE_matrix_mean(DataMatrix=tumo[,1:2],genes.by.pathway=pathway[1:10])
## [1] "Glycolysis_/ Gluconeogenesis"
## [1] "Citrate_cycle (TCA cycle)"
## [1] "Pentose_phosphate pathway"
## [1] "Pentose_and glucuronate interconversions"
## [1] "Fructose_and mannose metabolism"
## [1] "Galactose_metabolism"
## [1] "Ascorbate_and aldarate metabolism"
## [1] "Fatty_acid biosynthesis"
## [1] "Fatty_acid elongation"
## [1] "Fatty_acid degradation"

average: Average of genes for each pathway starting from a matrix of gene expression

Starting from a matrix of gene expression (rows are genes and columns are samples, TCGA data) the function average creates an average matrix (SXG: S are the samples and P the pathways) of gene expression for each pathway:

score_mean<-average(pathwayexpsubset=list_path_gene)

stdv: Standard deviations of genes for each pathway starting from a matrix of gene expression

Starting from a matrix of gene expression (rows are genes and columns are samples, TCGA data) the function stdv creates a standard deviation matrix of gene expression for each pathway:

score_st_dev<-stdv(gslist=list_path_gene)

Pathway cross-talk indexes: Score for pairwise pathways

eucdistcrtlk: Euclidean distance for cross-talk measure

Starting from a matrix of gene expression (rows are genes and columns are samples, TCGA data) the function eucdistcrtlk creates an euclidean distance matrix of gene expression for pairwise pathway.

score_euc_distance<-eucdistcrtlk(dataFilt=tumo[,1:2],pathway_exp=pathway[1:10])

dsscorecrtlk: Discriminating score for cross-talk measure

Starting from a matrix of gene expression (rows are genes and columns are samples, TCGA data) the function dsscorecrtlk creates an discriminating score matrix for pairwise pathway as measure of cross-talk. Discriminating score is given by |M1-M2|/S1+S2 where M1 and M2 are mean and S1 and S2 standard deviation of expression levels of genes in a pathway 1 and and in a pathway 2 .

cross_talk_st_dv<-dsscorecrtlk(dataFilt=tumo[,1:2],pathway_exp=pathway[1:10])

Selection of pathway cross-talk: Selection of pathway cross-talk

svm_classification: SVM classification

Given the substantial difference in the activities of many pathways between two classes (e.g. normal and cancer), we examined the effectiveness to classify the classes based on their pairwise pathway profiles. This function is used to find the interacting pathways that are altered in a particular pathology in terms of Area Under Curve (AUC).AUC was estimated by cross-validation method (k-fold cross-validation, k=10).It randomly selected some fraction of TCGA data (e.g. nf= 60; 60% of original dataset) to form the training set and then assigned the rest of the points to the testing set (40% of original dataset). For each pairwise pathway the user can obtain using the methods mentioned above a score matrix ( e.g.dev_std_crtlk ) and can focus on the pairs of pathways able to differentiate a particular subtype with respect to the normal type.

nf <- 60
res_class<-svm_classification(TCGA_matrix=score_euc_dista[1:30,],nfs=nf,
normal=colnames(norm[,1:10]),tumour=colnames(tumo[,1:10]))

IPPI: Driver genes for each pathway

The function IPPI, using pathways and networks data, calculates the driver genes for each pathway. Please see Cava et al. BMC Genomics 2017.

 DRIVER_SP<-IPPI(pathax=pathway_matrix[,1:3],netwa=netw_IPPI[1:50000,])

Visualization: Gene interactions and pathways

StarBioTrek presents several functions for the preparation to the visualization of gene-gene interactions and pathway cross-talk using the qgraph package (S. Epskamp, et al. 2012). The function plotcrosstalk prepares the data:

formatplot<-plotcrosstalk(pathway_plot=pathway[1:6],gs_expre=tumo)
library(qgraph)
## 
## Attaching package: 'qgraph'
## The following object is masked from 'package:graphite':
## 
##     pathways
## The following object is masked from 'package:StarBioTrek':
## 
##     pathways
qgraph(formatplot[[1]], minimum = 0.25, cut = 0.6, vsize = 5, groups = formatplot[[2]], legend = TRUE, borders = FALSE,layoutScale=c(0.8,0.8))

qgraph(formatplot[[1]],groups=formatplot[[2]], layout="spring", diag = FALSE,
cut = 0.6,legend.cex = 0.5,vsize = 6,layoutScale=c(0.8,0.8))

A circle can be generated using the function circleplot (Walter W, et al. 2015). A score for each gene can be assigned.

formatplot<-plotcrosstalk(pathway_plot=pathway[1:6],gs_expre=tumo)
score<-runif(length(formatplot[[2]]), min=-10, max=+10)
circleplot(preplot=formatplot,scoregene=score)

Session Information

sessionInfo()
## R version 4.3.1 (2023-06-16)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 22.04.3 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.18-bioc/R/lib/libRblas.so 
## LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.10.0
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_GB              LC_COLLATE=C              
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## time zone: America/New_York
## tzcode source: system (glibc)
## 
## attached base packages:
## [1] grid      stats4    stats     graphics  grDevices utils     datasets 
## [8] methods   base     
## 
## other attached packages:
##  [1] png_0.1-8            qgraph_1.9.5         graphite_1.48.0     
##  [4] StarBioTrek_1.28.0   miRNAtap_1.36.0      AnnotationDbi_1.64.0
##  [7] IRanges_2.36.0       S4Vectors_0.40.0     Biobase_2.62.0      
## [10] BiocGenerics_0.48.0  BiocStyle_2.30.0    
## 
## loaded via a namespace (and not attached):
##   [1] rstudioapi_0.15.0       jsonlite_1.8.7          magrittr_2.0.3         
##   [4] magick_2.8.1            rmarkdown_2.25          fs_1.6.3               
##   [7] zlibbioc_1.48.0         vctrs_0.6.4             ROCR_1.0-11            
##  [10] memoise_2.0.1           RCurl_1.98-1.12         base64enc_0.1-3        
##  [13] htmltools_0.5.6.1       usethis_2.2.2           curl_5.1.0             
##  [16] Formula_1.2-5           sass_0.4.7              bslib_0.5.1            
##  [19] htmlwidgets_1.6.2       desc_1.4.2              gsubfn_0.7             
##  [22] plyr_1.8.9              cachem_1.0.8            igraph_1.5.1           
##  [25] mime_0.12               lifecycle_1.0.3         pkgconfig_2.0.3        
##  [28] Matrix_1.6-1.1          R6_2.5.1                fastmap_1.1.1          
##  [31] GenomeInfoDbData_1.2.11 shiny_1.7.5.1           fdrtool_1.2.17         
##  [34] digest_0.6.33           colorspace_2.1-0        ps_1.7.5               
##  [37] chron_2.3-61            rprojroot_2.0.3         pkgload_1.3.3          
##  [40] miRNAtap.db_0.99.10     Hmisc_5.1-1             RSQLite_2.3.1          
##  [43] org.Hs.eg.db_3.18.0     fansi_1.0.5             abind_1.4-5            
##  [46] httr_1.4.7              compiler_4.3.1          proxy_0.4-27           
##  [49] remotes_2.4.2.1         bit64_4.0.5             withr_2.5.1            
##  [52] glasso_1.11             htmlTable_2.4.1         backports_1.4.1        
##  [55] DBI_1.1.3               psych_2.3.9             pkgbuild_1.4.2         
##  [58] rappdirs_0.3.3          sessioninfo_1.2.2       corpcor_1.6.10         
##  [61] gtools_3.9.4            pbivnorm_0.6.0          tools_4.3.1            
##  [64] foreign_0.8-85          httpuv_1.6.12           nnet_7.3-19            
##  [67] quadprog_1.5-8          glue_1.6.2              callr_3.7.3            
##  [70] nlme_3.1-163            promises_1.2.1          checkmate_2.2.0        
##  [73] cluster_2.1.4           SpidermiR_1.32.0        reshape2_1.4.4         
##  [76] generics_0.1.3          gtable_0.3.4            class_7.3-22           
##  [79] data.table_1.14.8       utf8_1.2.4              XVector_0.42.0         
##  [82] pillar_1.9.0            stringr_1.5.0           later_1.3.1            
##  [85] dplyr_1.1.3             lattice_0.22-5          bit_4.0.5              
##  [88] tidyselect_1.2.0        pbapply_1.7-2           Biostrings_2.70.0      
##  [91] miniUI_0.1.1.1          knitr_1.44              gridExtra_2.3          
##  [94] bookdown_0.36           sqldf_0.4-11            xfun_0.40              
##  [97] devtools_2.4.5          proto_1.0.0             stringi_1.7.12         
## [100] yaml_2.3.7              evaluate_0.22           MLmetrics_1.1.1        
## [103] tibble_3.2.1            BiocManager_1.30.22     graph_1.80.0           
## [106] cli_3.6.1               rpart_4.1.21            xtable_1.8-4           
## [109] lavaan_0.6-16           munsell_0.5.0           processx_3.8.2         
## [112] jquerylib_0.1.4         Rcpp_1.0.11             GenomeInfoDb_1.38.0    
## [115] parallel_4.3.1          ellipsis_0.3.2          ggplot2_3.4.4          
## [118] blob_1.2.4              prettyunits_1.2.0       jpeg_0.1-10            
## [121] profvis_0.3.8           urlchecker_1.0.1        bitops_1.0-7           
## [124] scales_1.2.1            e1071_1.7-13            purrr_1.0.2            
## [127] crayon_1.5.2            rlang_1.1.1             mnormt_2.1.1           
## [130] KEGGREST_1.42.0

References

Cancer Genome Atlas Research Network and others. 2012. “Comprehensive Molecular Characterization of Human Colon and Rectal Cancer.” https://doi.org/10.1038/nature11252.

Sales G, et al. 2012. “Graphite - a Bioconductor Package to Convert Pathway Topology to Gene Network.” https://doi.org/10.1186/1471-2105-13-20.

S. Epskamp, et al. 2012. “Qgraph Network Visualizations of Relationships in Psychometric Data.”

Walter W, et al. 2015. “GOplot an R Package for Visually Combining Expression Data with Functional Analysis.”

Warde-Farley D, et al. 2010. “The GeneMANIA Prediction Server Biological Network Integration for Gene Prioritization and Predicting Gene Function.”