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