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
btaurus kegg
btaurus pathbank
btaurus reactome
celegans kegg
celegans pathbank
celegans reactome
cfamiliaris kegg
cfamiliaris reactome
dmelanogaster kegg
dmelanogaster pathbank
dmelanogaster reactome
drerio kegg
drerio reactome
ecoli kegg
ecoli pathbank
ggallus kegg
ggallus reactome
hsapiens biocarta
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:

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