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 325 pathways"
## [1] "Querying.............  Citrate cycle (TCA cycle)   2 of 325 pathways"
## [1] "Querying.............  Pentose phosphate pathway   3 of 325 pathways"
## [1] "Querying.............  Pentose and glucuronate interconversions   4 of 325 pathways"
## [1] "Querying.............  Fructose and mannose metabolism   5 of 325 pathways"
## [1] "Querying.............  Galactose metabolism   6 of 325 pathways"
## [1] "Querying.............  Ascorbate and aldarate metabolism   7 of 325 pathways"
## [1] "Querying.............  Fatty acid biosynthesis   8 of 325 pathways"
## [1] "Querying.............  Fatty acid elongation   9 of 325 pathways"
## [1] "Querying.............  Fatty acid degradation   10 of 325 pathways"
## [1] "Querying.............  Steroid biosynthesis   11 of 325 pathways"
## [1] "Querying.............  Primary bile acid biosynthesis   12 of 325 pathways"
## [1] "Querying.............  Ubiquinone and other terpenoid-quinone biosynthesis   13 of 325 pathways"
## [1] "Querying.............  Steroid hormone biosynthesis   14 of 325 pathways"
## [1] "Querying.............  Oxidative phosphorylation   15 of 325 pathways"
## [1] "Querying.............  Arginine biosynthesis   16 of 325 pathways"
## [1] "Querying.............  Purine metabolism   17 of 325 pathways"
## [1] "Querying.............  Caffeine metabolism   18 of 325 pathways"
## [1] "Querying.............  Pyrimidine metabolism   19 of 325 pathways"
## [1] "Querying.............  Alanine, aspartate and glutamate metabolism   20 of 325 pathways"
## [1] "Querying.............  Glycine, serine and threonine metabolism   21 of 325 pathways"
## [1] "Querying.............  Cysteine and methionine metabolism   22 of 325 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine degradation   23 of 325 pathways"
## [1] "Querying.............  Lysine degradation   24 of 325 pathways"
## [1] "Querying.............  Arginine and proline metabolism   25 of 325 pathways"
## [1] "Querying.............  Histidine metabolism   26 of 325 pathways"
## [1] "Querying.............  Tyrosine metabolism   27 of 325 pathways"
## [1] "Querying.............  Phenylalanine metabolism   28 of 325 pathways"
## [1] "Querying.............  Tryptophan metabolism   29 of 325 pathways"
## [1] "Querying.............  Phenylalanine, tyrosine and tryptophan biosynthesis   30 of 325 pathways"
## [1] "Querying.............  beta-Alanine metabolism   31 of 325 pathways"
## [1] "Querying.............  Taurine and hypotaurine metabolism   32 of 325 pathways"
## [1] "Querying.............  Phosphonate and phosphinate metabolism   33 of 325 pathways"
## [1] "Querying.............  Selenocompound metabolism   34 of 325 pathways"
## [1] "Querying.............  D-Amino acid metabolism   35 of 325 pathways"
## [1] "Querying.............  Glutathione metabolism   36 of 325 pathways"
## [1] "Querying.............  Starch and sucrose metabolism   37 of 325 pathways"
## [1] "Querying.............  N-Glycan biosynthesis   38 of 325 pathways"
## [1] "Querying.............  Mucin type O-glycan biosynthesis   39 of 325 pathways"
## [1] "Querying.............  Various types of N-glycan biosynthesis   40 of 325 pathways"
## [1] "Querying.............  Mannose type O-glycan biosynthesis   41 of 325 pathways"
## [1] "Querying.............  Amino sugar and nucleotide sugar metabolism   42 of 325 pathways"
## [1] "Querying.............  Glycosaminoglycan degradation   43 of 325 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate   44 of 325 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - heparan sulfate / heparin   45 of 325 pathways"
## [1] "Querying.............  Glycerolipid metabolism   46 of 325 pathways"
## [1] "Querying.............  Inositol phosphate metabolism   47 of 325 pathways"
## [1] "Querying.............  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis   48 of 325 pathways"
## [1] "Querying.............  Glycerophospholipid metabolism   49 of 325 pathways"
## [1] "Querying.............  Ether lipid metabolism   50 of 325 pathways"
## [1] "Querying.............  Arachidonic acid metabolism   51 of 325 pathways"
## [1] "Querying.............  Linoleic acid metabolism   52 of 325 pathways"
## [1] "Querying.............  alpha-Linolenic acid metabolism   53 of 325 pathways"
## [1] "Querying.............  Sphingolipid metabolism   54 of 325 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - lacto and neolacto series   55 of 325 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - globo and isoglobo series   56 of 325 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - ganglio series   57 of 325 pathways"
## [1] "Querying.............  Pyruvate metabolism   58 of 325 pathways"
## [1] "Querying.............  Glyoxylate and dicarboxylate metabolism   59 of 325 pathways"
## [1] "Querying.............  Propanoate metabolism   60 of 325 pathways"
## [1] "Querying.............  Butanoate metabolism   61 of 325 pathways"
## [1] "Querying.............  One carbon pool by folate   62 of 325 pathways"
## [1] "Querying.............  Thiamine metabolism   63 of 325 pathways"
## [1] "Querying.............  Riboflavin metabolism   64 of 325 pathways"
## [1] "Querying.............  Vitamin B6 metabolism   65 of 325 pathways"
## [1] "Querying.............  Nicotinate and nicotinamide metabolism   66 of 325 pathways"
## [1] "Querying.............  Pantothenate and CoA biosynthesis   67 of 325 pathways"
## [1] "Querying.............  Biotin metabolism   68 of 325 pathways"
## [1] "Querying.............  Lipoic acid metabolism   69 of 325 pathways"
## [1] "Querying.............  Folate biosynthesis   70 of 325 pathways"
## [1] "Querying.............  Retinol metabolism   71 of 325 pathways"
## [1] "Querying.............  Porphyrin metabolism   72 of 325 pathways"
## [1] "Querying.............  Terpenoid backbone biosynthesis   73 of 325 pathways"
## [1] "Querying.............  Nitrogen metabolism   74 of 325 pathways"
## [1] "Querying.............  Sulfur metabolism   75 of 325 pathways"
## [1] "Querying.............  Aminoacyl-tRNA biosynthesis   76 of 325 pathways"
## [1] "Querying.............  Metabolism of xenobiotics by cytochrome P450   77 of 325 pathways"
## [1] "Querying.............  Drug metabolism - cytochrome P450   78 of 325 pathways"
## [1] "Querying.............  Drug metabolism - other enzymes   79 of 325 pathways"
## [1] "Querying.............  Biosynthesis of unsaturated fatty acids   80 of 325 pathways"
## [1] "Querying.............  Metabolic pathways   81 of 325 pathways"
## [1] "Querying.............  Carbon metabolism   82 of 325 pathways"
## [1] "Querying.............  2-Oxocarboxylic acid metabolism   83 of 325 pathways"
## [1] "Querying.............  Fatty acid metabolism   84 of 325 pathways"
## [1] "Querying.............  Biosynthesis of amino acids   85 of 325 pathways"
## [1] "Querying.............  Nucleotide metabolism   86 of 325 pathways"
## [1] "Querying.............  Biosynthesis of cofactors   87 of 325 pathways"
## [1] "Querying.............  Biosynthesis of nucleotide sugars   88 of 325 pathways"
## [1] "Querying.............  EGFR tyrosine kinase inhibitor resistance   89 of 325 pathways"
## [1] "Querying.............  Endocrine resistance   90 of 325 pathways"
## [1] "Querying.............  Antifolate resistance   91 of 325 pathways"
## [1] "Querying.............  Platinum drug resistance   92 of 325 pathways"
## [1] "Querying.............  mRNA surveillance pathway   93 of 325 pathways"
## [1] "Querying.............  RNA degradation   94 of 325 pathways"
## [1] "Querying.............  Viral life cycle - HIV-1   95 of 325 pathways"
## [1] "Querying.............  PPAR signaling pathway   96 of 325 pathways"
## [1] "Querying.............  Homologous recombination   97 of 325 pathways"
## [1] "Querying.............  Fanconi anemia pathway   98 of 325 pathways"
## [1] "Querying.............  MAPK signaling pathway   99 of 325 pathways"
## [1] "Querying.............  ErbB signaling pathway   100 of 325 pathways"
## [1] "Querying.............  Ras signaling pathway   101 of 325 pathways"
## [1] "Querying.............  Rap1 signaling pathway   102 of 325 pathways"
## [1] "Querying.............  Calcium signaling pathway   103 of 325 pathways"
## [1] "Querying.............  cGMP-PKG signaling pathway   104 of 325 pathways"
## [1] "Querying.............  cAMP signaling pathway   105 of 325 pathways"
## [1] "Querying.............  Cytokine-cytokine receptor interaction   106 of 325 pathways"
## [1] "Querying.............  Viral protein interaction with cytokine and cytokine receptor   107 of 325 pathways"
## [1] "Querying.............  Chemokine signaling pathway   108 of 325 pathways"
## [1] "Querying.............  NF-kappa B signaling pathway   109 of 325 pathways"
## [1] "Querying.............  HIF-1 signaling pathway   110 of 325 pathways"
## [1] "Querying.............  FoxO signaling pathway   111 of 325 pathways"
## [1] "Querying.............  Phosphatidylinositol signaling system   112 of 325 pathways"
## [1] "Querying.............  Sphingolipid signaling pathway   113 of 325 pathways"
## [1] "Querying.............  Phospholipase D signaling pathway   114 of 325 pathways"
## [1] "Querying.............  Neuroactive ligand-receptor interaction   115 of 325 pathways"
## [1] "Querying.............  Cell cycle   116 of 325 pathways"
## [1] "Querying.............  Oocyte meiosis   117 of 325 pathways"
## [1] "Querying.............  p53 signaling pathway   118 of 325 pathways"
## [1] "Querying.............  Sulfur relay system   119 of 325 pathways"
## [1] "Querying.............  SNARE interactions in vesicular transport   120 of 325 pathways"
## [1] "Querying.............  Autophagy - other   121 of 325 pathways"
## [1] "Querying.............  Mitophagy - animal   122 of 325 pathways"
## [1] "Querying.............  Autophagy - animal   123 of 325 pathways"
## [1] "Querying.............  Protein processing in endoplasmic reticulum   124 of 325 pathways"
## [1] "Querying.............  Endocytosis   125 of 325 pathways"
## [1] "Querying.............  Phagosome   126 of 325 pathways"
## [1] "Querying.............  Peroxisome   127 of 325 pathways"
## [1] "Querying.............  mTOR signaling pathway   128 of 325 pathways"
## [1] "Querying.............  PI3K-Akt signaling pathway   129 of 325 pathways"
## [1] "Querying.............  AMPK signaling pathway   130 of 325 pathways"
## [1] "Querying.............  Apoptosis   131 of 325 pathways"
## [1] "Querying.............  Longevity regulating pathway   132 of 325 pathways"
## [1] "Querying.............  Longevity regulating pathway - multiple species   133 of 325 pathways"
## [1] "Querying.............  Apoptosis - multiple species   134 of 325 pathways"
## [1] "Querying.............  Ferroptosis   135 of 325 pathways"
## [1] "Querying.............  Necroptosis   136 of 325 pathways"
## [1] "Querying.............  Cellular senescence   137 of 325 pathways"
## [1] "Querying.............  Cardiac muscle contraction   138 of 325 pathways"
## [1] "Querying.............  Adrenergic signaling in cardiomyocytes   139 of 325 pathways"
## [1] "Querying.............  Vascular smooth muscle contraction   140 of 325 pathways"
## [1] "Querying.............  Wnt signaling pathway   141 of 325 pathways"
## [1] "Querying.............  Notch signaling pathway   142 of 325 pathways"
## [1] "Querying.............  Hedgehog signaling pathway   143 of 325 pathways"
## [1] "Querying.............  TGF-beta signaling pathway   144 of 325 pathways"
## [1] "Querying.............  Axon guidance   145 of 325 pathways"
## [1] "Querying.............  VEGF signaling pathway   146 of 325 pathways"
## [1] "Querying.............  Apelin signaling pathway   147 of 325 pathways"
## [1] "Querying.............  Osteoclast differentiation   148 of 325 pathways"
## [1] "Querying.............  Hippo signaling pathway   149 of 325 pathways"
## [1] "Querying.............  Hippo signaling pathway - multiple species   150 of 325 pathways"
## [1] "Querying.............  Focal adhesion   151 of 325 pathways"
## [1] "Querying.............  ECM-receptor interaction   152 of 325 pathways"
## [1] "Querying.............  Cell adhesion molecules   153 of 325 pathways"
## [1] "Querying.............  Adherens junction   154 of 325 pathways"
## [1] "Querying.............  Tight junction   155 of 325 pathways"
## [1] "Querying.............  Gap junction   156 of 325 pathways"
## [1] "Querying.............  Signaling pathways regulating pluripotency of stem cells   157 of 325 pathways"
## [1] "Querying.............  Complement and coagulation cascades   158 of 325 pathways"
## [1] "Querying.............  Platelet activation   159 of 325 pathways"
## [1] "Querying.............  Antigen processing and presentation   160 of 325 pathways"
## [1] "Querying.............  Neutrophil extracellular trap formation   161 of 325 pathways"
## [1] "Querying.............  Renin-angiotensin system   162 of 325 pathways"
## [1] "Querying.............  Toll-like receptor signaling pathway   163 of 325 pathways"
## [1] "Querying.............  NOD-like receptor signaling pathway   164 of 325 pathways"
## [1] "Querying.............  RIG-I-like receptor signaling pathway   165 of 325 pathways"
## [1] "Querying.............  Cytosolic DNA-sensing pathway   166 of 325 pathways"
## [1] "Querying.............  C-type lectin receptor signaling pathway   167 of 325 pathways"
## [1] "Querying.............  JAK-STAT signaling pathway   168 of 325 pathways"
## [1] "Querying.............  Natural killer cell mediated cytotoxicity   169 of 325 pathways"
## [1] "Querying.............  IL-17 signaling pathway   170 of 325 pathways"
## [1] "Querying.............  Th1 and Th2 cell differentiation   171 of 325 pathways"
## [1] "Querying.............  Th17 cell differentiation   172 of 325 pathways"
## [1] "Querying.............  T cell receptor signaling pathway   173 of 325 pathways"
## [1] "Querying.............  B cell receptor signaling pathway   174 of 325 pathways"
## [1] "Querying.............  Fc epsilon RI signaling pathway   175 of 325 pathways"
## [1] "Querying.............  Fc gamma R-mediated phagocytosis   176 of 325 pathways"
## [1] "Querying.............  TNF signaling pathway   177 of 325 pathways"
## [1] "Querying.............  Leukocyte transendothelial migration   178 of 325 pathways"
## [1] "Querying.............  Intestinal immune network for IgA production   179 of 325 pathways"
## [1] "Querying.............  Circadian rhythm   180 of 325 pathways"
## [1] "Querying.............  Circadian entrainment   181 of 325 pathways"
## [1] "Querying.............  Thermogenesis   182 of 325 pathways"
## [1] "Querying.............  Long-term potentiation   183 of 325 pathways"
## [1] "Querying.............  Synaptic vesicle cycle   184 of 325 pathways"
## [1] "Querying.............  Neurotrophin signaling pathway   185 of 325 pathways"
## [1] "Querying.............  Retrograde endocannabinoid signaling   186 of 325 pathways"
## [1] "Querying.............  Glutamatergic synapse   187 of 325 pathways"
## [1] "Querying.............  Cholinergic synapse   188 of 325 pathways"
## [1] "Querying.............  Serotonergic synapse   189 of 325 pathways"
## [1] "Querying.............  GABAergic synapse   190 of 325 pathways"
## [1] "Querying.............  Dopaminergic synapse   191 of 325 pathways"
## [1] "Querying.............  Long-term depression   192 of 325 pathways"
## [1] "Querying.............  Olfactory transduction   193 of 325 pathways"
## [1] "Querying.............  Taste transduction   194 of 325 pathways"
## [1] "Querying.............  Phototransduction   195 of 325 pathways"
## [1] "Querying.............  Inflammatory mediator regulation of TRP channels   196 of 325 pathways"
## [1] "Querying.............  Regulation of actin cytoskeleton   197 of 325 pathways"
## [1] "Querying.............  Insulin signaling pathway   198 of 325 pathways"
## [1] "Querying.............  Insulin secretion   199 of 325 pathways"
## [1] "Querying.............  GnRH signaling pathway   200 of 325 pathways"
## [1] "Querying.............  Ovarian steroidogenesis   201 of 325 pathways"
## [1] "Querying.............  Progesterone-mediated oocyte maturation   202 of 325 pathways"
## [1] "Querying.............  Estrogen signaling pathway   203 of 325 pathways"
## [1] "Querying.............  Melanogenesis   204 of 325 pathways"
## [1] "Querying.............  Prolactin signaling pathway   205 of 325 pathways"
## [1] "Querying.............  Thyroid hormone synthesis   206 of 325 pathways"
## [1] "Querying.............  Thyroid hormone signaling pathway   207 of 325 pathways"
## [1] "Querying.............  Adipocytokine signaling pathway   208 of 325 pathways"
## [1] "Querying.............  Oxytocin signaling pathway   209 of 325 pathways"
## [1] "Querying.............  Glucagon signaling pathway   210 of 325 pathways"
## [1] "Querying.............  Regulation of lipolysis in adipocytes   211 of 325 pathways"
## [1] "Querying.............  Renin secretion   212 of 325 pathways"
## [1] "Querying.............  Aldosterone synthesis and secretion   213 of 325 pathways"
## [1] "Querying.............  Relaxin signaling pathway   214 of 325 pathways"
## [1] "Querying.............  Cortisol synthesis and secretion   215 of 325 pathways"
## [1] "Querying.............  Parathyroid hormone synthesis, secretion and action   216 of 325 pathways"
## [1] "Querying.............  GnRH secretion   217 of 325 pathways"
## [1] "Querying.............  Type II diabetes mellitus   218 of 325 pathways"
## [1] "Querying.............  Insulin resistance   219 of 325 pathways"
## [1] "Querying.............  Non-alcoholic fatty liver disease   220 of 325 pathways"
## [1] "Querying.............  AGE-RAGE signaling pathway in diabetic complications   221 of 325 pathways"
## [1] "Querying.............  Cushing syndrome   222 of 325 pathways"
## [1] "Querying.............  Growth hormone synthesis, secretion and action   223 of 325 pathways"
## [1] "Querying.............  Alcoholic liver disease   224 of 325 pathways"
## [1] "Querying.............  Type I diabetes mellitus   225 of 325 pathways"
## [1] "Querying.............  Maturity onset diabetes of the young   226 of 325 pathways"
## [1] "Querying.............  Aldosterone-regulated sodium reabsorption   227 of 325 pathways"
## [1] "Querying.............  Endocrine and other factor-regulated calcium reabsorption   228 of 325 pathways"
## [1] "Querying.............  Vasopressin-regulated water reabsorption   229 of 325 pathways"
## [1] "Querying.............  Proximal tubule bicarbonate reclamation   230 of 325 pathways"
## [1] "Querying.............  Salivary secretion   231 of 325 pathways"
## [1] "Querying.............  Gastric acid secretion   232 of 325 pathways"
## [1] "Querying.............  Pancreatic secretion   233 of 325 pathways"
## [1] "Querying.............  Carbohydrate digestion and absorption   234 of 325 pathways"
## [1] "Querying.............  Fat digestion and absorption   235 of 325 pathways"
## [1] "Querying.............  Bile secretion   236 of 325 pathways"
## [1] "Querying.............  Vitamin digestion and absorption   237 of 325 pathways"
## [1] "Querying.............  Mineral absorption   238 of 325 pathways"
## [1] "Querying.............  Cholesterol metabolism   239 of 325 pathways"
## [1] "Querying.............  Alzheimer disease   240 of 325 pathways"
## [1] "Querying.............  Parkinson disease   241 of 325 pathways"
## [1] "Querying.............  Amyotrophic lateral sclerosis   242 of 325 pathways"
## [1] "Querying.............  Huntington disease   243 of 325 pathways"
## [1] "Querying.............  Spinocerebellar ataxia   244 of 325 pathways"
## [1] "Querying.............  Prion disease   245 of 325 pathways"
## [1] "Querying.............  Pathways of neurodegeneration - multiple diseases   246 of 325 pathways"
## [1] "Querying.............  Cocaine addiction   247 of 325 pathways"
## [1] "Querying.............  Amphetamine addiction   248 of 325 pathways"
## [1] "Querying.............  Morphine addiction   249 of 325 pathways"
## [1] "Querying.............  Alcoholism   250 of 325 pathways"
## [1] "Querying.............  Bacterial invasion of epithelial cells   251 of 325 pathways"
## [1] "Querying.............  Vibrio cholerae infection   252 of 325 pathways"
## [1] "Querying.............  Epithelial cell signaling in Helicobacter pylori infection   253 of 325 pathways"
## [1] "Querying.............  Pathogenic Escherichia coli infection   254 of 325 pathways"
## [1] "Querying.............  Shigellosis   255 of 325 pathways"
## [1] "Querying.............  Salmonella infection   256 of 325 pathways"
## [1] "Querying.............  Pertussis   257 of 325 pathways"
## [1] "Querying.............  Legionellosis   258 of 325 pathways"
## [1] "Querying.............  Yersinia infection   259 of 325 pathways"
## [1] "Querying.............  Leishmaniasis   260 of 325 pathways"
## [1] "Querying.............  Chagas disease   261 of 325 pathways"
## [1] "Querying.............  African trypanosomiasis   262 of 325 pathways"
## [1] "Querying.............  Malaria   263 of 325 pathways"
## [1] "Querying.............  Toxoplasmosis   264 of 325 pathways"
## [1] "Querying.............  Amoebiasis   265 of 325 pathways"
## [1] "Querying.............  Staphylococcus aureus infection   266 of 325 pathways"
## [1] "Querying.............  Tuberculosis   267 of 325 pathways"
## [1] "Querying.............  Hepatitis C   268 of 325 pathways"
## [1] "Querying.............  Hepatitis B   269 of 325 pathways"
## [1] "Querying.............  Measles   270 of 325 pathways"
## [1] "Querying.............  Human cytomegalovirus infection   271 of 325 pathways"
## [1] "Querying.............  Influenza A   272 of 325 pathways"
## [1] "Querying.............  Human papillomavirus infection   273 of 325 pathways"
## [1] "Querying.............  Human T-cell leukemia virus 1 infection   274 of 325 pathways"
## [1] "Querying.............  Kaposi sarcoma-associated herpesvirus infection   275 of 325 pathways"
## [1] "Querying.............  Herpes simplex virus 1 infection   276 of 325 pathways"
## [1] "Querying.............  Epstein-Barr virus infection   277 of 325 pathways"
## [1] "Querying.............  Human immunodeficiency virus 1 infection   278 of 325 pathways"
## [1] "Querying.............  Coronavirus disease - COVID-19   279 of 325 pathways"
## [1] "Querying.............  Pathways in cancer   280 of 325 pathways"
## [1] "Querying.............  Transcriptional misregulation in cancer   281 of 325 pathways"
## [1] "Querying.............  Viral carcinogenesis   282 of 325 pathways"
## [1] "Querying.............  Chemical carcinogenesis - DNA adducts   283 of 325 pathways"
## [1] "Querying.............  Proteoglycans in cancer   284 of 325 pathways"
## [1] "Querying.............  MicroRNAs in cancer   285 of 325 pathways"
## [1] "Querying.............  Chemical carcinogenesis - receptor activation   286 of 325 pathways"
## [1] "Querying.............  Chemical carcinogenesis - reactive oxygen species   287 of 325 pathways"
## [1] "Querying.............  Colorectal cancer   288 of 325 pathways"
## [1] "Querying.............  Renal cell carcinoma   289 of 325 pathways"
## [1] "Querying.............  Pancreatic cancer   290 of 325 pathways"
## [1] "Querying.............  Endometrial cancer   291 of 325 pathways"
## [1] "Querying.............  Glioma   292 of 325 pathways"
## [1] "Querying.............  Prostate cancer   293 of 325 pathways"
## [1] "Querying.............  Thyroid cancer   294 of 325 pathways"
## [1] "Querying.............  Basal cell carcinoma   295 of 325 pathways"
## [1] "Querying.............  Melanoma   296 of 325 pathways"
## [1] "Querying.............  Bladder cancer   297 of 325 pathways"
## [1] "Querying.............  Chronic myeloid leukemia   298 of 325 pathways"
## [1] "Querying.............  Acute myeloid leukemia   299 of 325 pathways"
## [1] "Querying.............  Small cell lung cancer   300 of 325 pathways"
## [1] "Querying.............  Non-small cell lung cancer   301 of 325 pathways"
## [1] "Querying.............  Breast cancer   302 of 325 pathways"
## [1] "Querying.............  Hepatocellular carcinoma   303 of 325 pathways"
## [1] "Querying.............  Gastric cancer   304 of 325 pathways"
## [1] "Querying.............  Central carbon metabolism in cancer   305 of 325 pathways"
## [1] "Querying.............  Choline metabolism in cancer   306 of 325 pathways"
## [1] "Querying.............  PD-L1 expression and PD-1 checkpoint pathway in cancer   307 of 325 pathways"
## [1] "Querying.............  Asthma   308 of 325 pathways"
## [1] "Querying.............  Autoimmune thyroid disease   309 of 325 pathways"
## [1] "Querying.............  Inflammatory bowel disease   310 of 325 pathways"
## [1] "Querying.............  Systemic lupus erythematosus   311 of 325 pathways"
## [1] "Querying.............  Rheumatoid arthritis   312 of 325 pathways"
## [1] "Querying.............  Allograft rejection   313 of 325 pathways"
## [1] "Querying.............  Graft-versus-host disease   314 of 325 pathways"
## [1] "Querying.............  Hypertrophic cardiomyopathy   315 of 325 pathways"
## [1] "Querying.............  Arrhythmogenic right ventricular cardiomyopathy   316 of 325 pathways"
## [1] "Querying.............  Dilated cardiomyopathy   317 of 325 pathways"
## [1] "Querying.............  Diabetic cardiomyopathy   318 of 325 pathways"
## [1] "Querying.............  Viral myocarditis   319 of 325 pathways"
## [1] "Querying.............  Lipid and atherosclerosis   320 of 325 pathways"
## [1] "Querying.............  Fluid shear stress and atherosclerosis   321 of 325 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine biosynthesis   322 of 325 pathways"
## [1] "Querying.............  Neomycin, kanamycin and gentamicin biosynthesis   323 of 325 pathways"
## [1] "Querying.............  Protein digestion and absorption   324 of 325 pathways"
## [1] "Querying.............  Nicotine addiction   325 of 325 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 4.3.0 RC (2023-04-13 r84269)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 22.04.2 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.17-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_1.9.4         graphite_1.46.0     
##  [4] StarBioTrek_1.26.0   miRNAtap_1.34.0      AnnotationDbi_1.62.0
##  [7] IRanges_2.34.0       S4Vectors_0.38.0     Biobase_2.60.0      
## [10] BiocGenerics_0.46.0  BiocStyle_2.28.0    
## 
## loaded via a namespace (and not attached):
##   [1] rstudioapi_0.14         jsonlite_1.8.4          magrittr_2.0.3         
##   [4] magick_2.7.4            rmarkdown_2.21          fs_1.6.2               
##   [7] zlibbioc_1.46.0         vctrs_0.6.2             ROCR_1.0-11            
##  [10] memoise_2.0.1           RCurl_1.98-1.12         base64enc_0.1-3        
##  [13] htmltools_0.5.5         usethis_2.1.6           curl_5.0.0             
##  [16] Formula_1.2-5           sass_0.4.5              bslib_0.4.2            
##  [19] htmlwidgets_1.6.2       desc_1.4.2              gsubfn_0.7             
##  [22] plyr_1.8.8              cachem_1.0.7            igraph_1.4.2           
##  [25] mime_0.12               lifecycle_1.0.3         pkgconfig_2.0.3        
##  [28] Matrix_1.5-4            R6_2.5.1                fastmap_1.1.1          
##  [31] GenomeInfoDbData_1.2.10 shiny_1.7.4             fdrtool_1.2.17         
##  [34] digest_0.6.31           colorspace_2.1-0        ps_1.7.5               
##  [37] chron_2.3-60            rprojroot_2.0.3         pkgload_1.3.2          
##  [40] miRNAtap.db_0.99.10     Hmisc_5.0-1             RSQLite_2.3.1          
##  [43] org.Hs.eg.db_3.17.0     fansi_1.0.4             abind_1.4-5            
##  [46] httr_1.4.5              compiler_4.3.0          proxy_0.4-27           
##  [49] remotes_2.4.2           bit64_4.0.5             withr_2.5.0            
##  [52] glasso_1.11             htmlTable_2.4.1         backports_1.4.1        
##  [55] DBI_1.1.3               psych_2.3.3             highr_0.10             
##  [58] pkgbuild_1.4.0          rappdirs_0.3.3          sessioninfo_1.2.2      
##  [61] corpcor_1.6.10          gtools_3.9.4            pbivnorm_0.6.0         
##  [64] tools_4.3.0             foreign_0.8-84          httpuv_1.6.9           
##  [67] nnet_7.3-18             quadprog_1.5-8          glue_1.6.2             
##  [70] callr_3.7.3             nlme_3.1-162            promises_1.2.0.1       
##  [73] checkmate_2.1.0         cluster_2.1.4           SpidermiR_1.30.0       
##  [76] reshape2_1.4.4          generics_0.1.3          gtable_0.3.3           
##  [79] class_7.3-21            data.table_1.14.8       utf8_1.2.3             
##  [82] XVector_0.40.0          pillar_1.9.0            stringr_1.5.0          
##  [85] later_1.3.0             dplyr_1.1.2             lattice_0.21-8         
##  [88] bit_4.0.5               tidyselect_1.2.0        pbapply_1.7-0          
##  [91] Biostrings_2.68.0       miniUI_0.1.1.1          knitr_1.42             
##  [94] gridExtra_2.3           bookdown_0.33           sqldf_0.4-11           
##  [97] xfun_0.39               devtools_2.4.5          proto_1.0.0            
## [100] stringi_1.7.12          yaml_2.3.7              evaluate_0.20          
## [103] MLmetrics_1.1.1         tibble_3.2.1            BiocManager_1.30.20    
## [106] graph_1.78.0            cli_3.6.1               rpart_4.1.19           
## [109] xtable_1.8-4            lavaan_0.6-15           munsell_0.5.0          
## [112] processx_3.8.1          jquerylib_0.1.4         Rcpp_1.0.10            
## [115] GenomeInfoDb_1.36.0     parallel_4.3.0          ellipsis_0.3.2         
## [118] ggplot2_3.4.2           blob_1.2.4              prettyunits_1.1.1      
## [121] jpeg_0.1-10             profvis_0.3.7           urlchecker_1.0.1       
## [124] bitops_1.0-7            scales_1.2.1            e1071_1.7-13           
## [127] purrr_1.0.1             crayon_1.5.2            rlang_1.1.0            
## [130] mnormt_2.1.1            KEGGREST_1.40.0

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.”