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

## Registered S3 methods overwritten by 'huge':
##   method    from   
##   plot.sim  BDgraph
##   print.sim BDgraph
## 
## Attaching package: 'qgraph'
## The following object is masked from 'package:graphite':
## 
##     pathways
## The following object is masked from 'package:StarBioTrek':
## 
##     pathways

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

Session Information

## R version 3.6.1 (2019-07-05)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 18.04.3 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.10-bioc/R/lib/libRblas.so
## LAPACK: /home/biocbuild/bbs-3.10-bioc/R/lib/libRlapack.so
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=C              
##  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
##  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
##  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
## [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
## 
## attached base packages:
##  [1] grid      parallel  stats4    stats     graphics  grDevices utils    
##  [8] datasets  methods   base     
## 
## other attached packages:
##  [1] png_0.1-7            qgraph_1.6.3         org.Hs.eg.db_3.10.0 
##  [4] graphite_1.32.0      StarBioTrek_1.12.0   miRNAtap_1.20.0     
##  [7] AnnotationDbi_1.48.0 IRanges_2.20.0       S4Vectors_0.24.0    
## [10] Biobase_2.46.0       BiocGenerics_0.32.0  BiocStyle_2.14.0    
## 
## loaded via a namespace (and not attached):
##   [1] colorspace_1.4-1    rjson_0.2.20        ellipsis_0.3.0     
##   [4] class_7.3-15        rprojroot_1.3-2     htmlTable_1.13.2   
##   [7] corpcor_1.6.9       base64enc_0.1-3     fs_1.3.1           
##  [10] rstudioapi_0.10     lavaan_0.6-5        remotes_2.1.0      
##  [13] bit64_0.9-7         sqldf_0.4-11        splines_3.6.1      
##  [16] mnormt_1.5-5        knitr_1.25          glasso_1.11        
##  [19] pkgload_1.0.2       zeallot_0.1.0       Formula_1.2-3      
##  [22] jsonlite_1.6        cluster_2.1.0       graph_1.64.0       
##  [25] BiocManager_1.30.9  compiler_3.6.1      httr_1.4.1         
##  [28] backports_1.1.5     assertthat_0.2.1    Matrix_1.2-17      
##  [31] lazyeval_0.2.2      cli_1.1.0           acepack_1.4.1      
##  [34] visNetwork_2.0.8    htmltools_0.4.0     prettyunits_1.0.2  
##  [37] tools_3.6.1         igraph_1.2.4.1      gtable_0.3.0       
##  [40] glue_1.3.1          reshape2_1.4.3      dplyr_0.8.3        
##  [43] rappdirs_0.3.1      Rcpp_1.0.2          vctrs_0.2.0        
##  [46] nlme_3.1-141        gdata_2.18.0        psych_1.8.12       
##  [49] xfun_0.10           stringr_1.4.0       networkD3_0.4      
##  [52] ps_1.3.0            proto_1.0.0         testthat_2.2.1     
##  [55] ggm_2.3             gtools_3.8.1        devtools_2.2.1     
##  [58] MASS_7.3-51.4       MLmetrics_1.1.1     scales_1.0.0       
##  [61] BDgraph_2.61        huge_1.3.4          RColorBrewer_1.1-2 
##  [64] yaml_2.2.0          curl_4.2            pbapply_1.4-2      
##  [67] memoise_1.1.0       gridExtra_2.3       miRNAtap.db_0.99.10
##  [70] ggplot2_3.2.1       rpart_4.1-15        latticeExtra_0.6-28
##  [73] stringi_1.4.3       RSQLite_2.1.2       highr_0.8          
##  [76] desc_1.2.0          e1071_1.7-2         checkmate_1.9.4    
##  [79] caTools_1.17.1.2    pkgbuild_1.0.6      chron_2.3-54       
##  [82] d3Network_0.5.2.1   rlang_0.4.1         pkgconfig_2.0.3    
##  [85] bitops_1.0-6        evaluate_0.14       lattice_0.20-38    
##  [88] ROCR_1.0-7          purrr_0.3.3         htmlwidgets_1.5.1  
##  [91] bit_1.1-14          processx_3.4.1      tidyselect_0.2.5   
##  [94] plyr_1.8.4          magrittr_1.5        bookdown_0.14      
##  [97] R6_2.4.0            gplots_3.0.1.1      Hmisc_4.2-0        
## [100] DBI_1.0.0           whisker_0.4         foreign_0.8-72     
## [103] gsubfn_0.7          pillar_1.4.2        withr_2.1.2        
## [106] abind_1.4-5         nnet_7.3-12         survival_2.44-1.1  
## [109] tibble_2.1.3        crayon_1.3.4        fdrtool_1.2.15     
## [112] KernSmooth_2.23-16  rmarkdown_1.16      jpeg_0.1-8.1       
## [115] usethis_1.5.1       pbivnorm_0.6.0      data.table_1.12.6  
## [118] blob_1.2.0          callr_3.3.2         digest_0.6.22      
## [121] munsell_0.5.0       SpidermiR_1.16.0    sessioninfo_1.1.1

References

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

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

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

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

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