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.

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)


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:

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

GetPathData: Get genes inside pathways

The user can identify the genes inside the pathways of interest

GetPathNet: Get interacting genes inside pathways

GetPathNet generates a list of interacting genes for each pathway

ConvertedIDgenes: Get genes inside pathways

The user can convert the gene ID into GeneSymbol

## '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
## '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.

## [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.

## [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.

## [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:

## [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.

## [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:

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:

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.

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 .

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.

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.

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:

## 
## Attaching package: 'qgraph'
## The following object is masked from 'package:graphite':
## 
##     pathways
## The following object is masked from 'package:StarBioTrek':
## 
##     pathways