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 307 pathways"
## [1] "Querying.............  Citrate cycle (TCA cycle)   2 of 307 pathways"
## [1] "Querying.............  Pentose phosphate pathway   3 of 307 pathways"
## [1] "Querying.............  Pentose and glucuronate interconversions   4 of 307 pathways"
## [1] "Querying.............  Fructose and mannose metabolism   5 of 307 pathways"
## [1] "Querying.............  Galactose metabolism   6 of 307 pathways"
## [1] "Querying.............  Ascorbate and aldarate metabolism   7 of 307 pathways"
## [1] "Querying.............  Fatty acid biosynthesis   8 of 307 pathways"
## [1] "Querying.............  Fatty acid elongation   9 of 307 pathways"
## [1] "Querying.............  Fatty acid degradation   10 of 307 pathways"
## [1] "Querying.............  Synthesis and degradation of ketone bodies   11 of 307 pathways"
## [1] "Querying.............  Steroid biosynthesis   12 of 307 pathways"
## [1] "Querying.............  Primary bile acid biosynthesis   13 of 307 pathways"
## [1] "Querying.............  Ubiquinone and other terpenoid-quinone biosynthesis   14 of 307 pathways"
## [1] "Querying.............  Steroid hormone biosynthesis   15 of 307 pathways"
## [1] "Querying.............  Oxidative phosphorylation   16 of 307 pathways"
## [1] "Querying.............  Arginine biosynthesis   17 of 307 pathways"
## [1] "Querying.............  Purine metabolism   18 of 307 pathways"
## [1] "Querying.............  Caffeine metabolism   19 of 307 pathways"
## [1] "Querying.............  Pyrimidine metabolism   20 of 307 pathways"
## [1] "Querying.............  Alanine, aspartate and glutamate metabolism   21 of 307 pathways"
## [1] "Querying.............  Glycine, serine and threonine metabolism   22 of 307 pathways"
## [1] "Querying.............  Cysteine and methionine metabolism   23 of 307 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine degradation   24 of 307 pathways"
## [1] "Querying.............  Lysine degradation   25 of 307 pathways"
## [1] "Querying.............  Arginine and proline metabolism   26 of 307 pathways"
## [1] "Querying.............  Histidine metabolism   27 of 307 pathways"
## [1] "Querying.............  Tyrosine metabolism   28 of 307 pathways"
## [1] "Querying.............  Phenylalanine metabolism   29 of 307 pathways"
## [1] "Querying.............  Tryptophan metabolism   30 of 307 pathways"
## [1] "Querying.............  Phenylalanine, tyrosine and tryptophan biosynthesis   31 of 307 pathways"
## [1] "Querying.............  beta-Alanine metabolism   32 of 307 pathways"
## [1] "Querying.............  Taurine and hypotaurine metabolism   33 of 307 pathways"
## [1] "Querying.............  Phosphonate and phosphinate metabolism   34 of 307 pathways"
## [1] "Querying.............  Selenocompound metabolism   35 of 307 pathways"
## [1] "Querying.............  D-Glutamine and D-glutamate metabolism   36 of 307 pathways"
## [1] "Querying.............  Glutathione metabolism   37 of 307 pathways"
## [1] "Querying.............  Starch and sucrose metabolism   38 of 307 pathways"
## [1] "Querying.............  N-Glycan biosynthesis   39 of 307 pathways"
## [1] "Querying.............  Mucin type O-glycan biosynthesis   40 of 307 pathways"
## [1] "Querying.............  Various types of N-glycan biosynthesis   41 of 307 pathways"
## [1] "Querying.............  Mannose type O-glycan biosynthesis   42 of 307 pathways"
## [1] "Querying.............  Amino sugar and nucleotide sugar metabolism   43 of 307 pathways"
## [1] "Querying.............  Glycosaminoglycan degradation   44 of 307 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate   45 of 307 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - heparan sulfate / heparin   46 of 307 pathways"
## [1] "Querying.............  Glycerolipid metabolism   47 of 307 pathways"
## [1] "Querying.............  Inositol phosphate metabolism   48 of 307 pathways"
## [1] "Querying.............  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis   49 of 307 pathways"
## [1] "Querying.............  Glycerophospholipid metabolism   50 of 307 pathways"
## [1] "Querying.............  Ether lipid metabolism   51 of 307 pathways"
## [1] "Querying.............  Arachidonic acid metabolism   52 of 307 pathways"
## [1] "Querying.............  Linoleic acid metabolism   53 of 307 pathways"
## [1] "Querying.............  alpha-Linolenic acid metabolism   54 of 307 pathways"
## [1] "Querying.............  Sphingolipid metabolism   55 of 307 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - lacto and neolacto series   56 of 307 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - globo and isoglobo series   57 of 307 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - ganglio series   58 of 307 pathways"
## [1] "Querying.............  Pyruvate metabolism   59 of 307 pathways"
## [1] "Querying.............  Glyoxylate and dicarboxylate metabolism   60 of 307 pathways"
## [1] "Querying.............  Propanoate metabolism   61 of 307 pathways"
## [1] "Querying.............  Butanoate metabolism   62 of 307 pathways"
## [1] "Querying.............  One carbon pool by folate   63 of 307 pathways"
## [1] "Querying.............  Thiamine metabolism   64 of 307 pathways"
## [1] "Querying.............  Riboflavin metabolism   65 of 307 pathways"
## [1] "Querying.............  Vitamin B6 metabolism   66 of 307 pathways"
## [1] "Querying.............  Nicotinate and nicotinamide metabolism   67 of 307 pathways"
## [1] "Querying.............  Pantothenate and CoA biosynthesis   68 of 307 pathways"
## [1] "Querying.............  Biotin metabolism   69 of 307 pathways"
## [1] "Querying.............  Lipoic acid metabolism   70 of 307 pathways"
## [1] "Querying.............  Folate biosynthesis   71 of 307 pathways"
## [1] "Querying.............  Retinol metabolism   72 of 307 pathways"
## [1] "Querying.............  Porphyrin and chlorophyll metabolism   73 of 307 pathways"
## [1] "Querying.............  Terpenoid backbone biosynthesis   74 of 307 pathways"
## [1] "Querying.............  Nitrogen metabolism   75 of 307 pathways"
## [1] "Querying.............  Sulfur metabolism   76 of 307 pathways"
## [1] "Querying.............  Aminoacyl-tRNA biosynthesis   77 of 307 pathways"
## [1] "Querying.............  Metabolism of xenobiotics by cytochrome P450   78 of 307 pathways"
## [1] "Querying.............  Drug metabolism - cytochrome P450   79 of 307 pathways"
## [1] "Querying.............  Drug metabolism - other enzymes   80 of 307 pathways"
## [1] "Querying.............  Ribosome biogenesis in eukaryotes   81 of 307 pathways"
## [1] "Querying.............  RNA transport   82 of 307 pathways"
## [1] "Querying.............  mRNA surveillance pathway   83 of 307 pathways"
## [1] "Querying.............  RNA degradation   84 of 307 pathways"
## [1] "Querying.............  PPAR signaling pathway   85 of 307 pathways"
## [1] "Querying.............  Homologous recombination   86 of 307 pathways"
## [1] "Querying.............  Fanconi anemia pathway   87 of 307 pathways"
## [1] "Querying.............  MAPK signaling pathway   88 of 307 pathways"
## [1] "Querying.............  ErbB signaling pathway   89 of 307 pathways"
## [1] "Querying.............  Ras signaling pathway   90 of 307 pathways"
## [1] "Querying.............  Rap1 signaling pathway   91 of 307 pathways"
## [1] "Querying.............  Calcium signaling pathway   92 of 307 pathways"
## [1] "Querying.............  cGMP-PKG signaling pathway   93 of 307 pathways"
## [1] "Querying.............  cAMP signaling pathway   94 of 307 pathways"
## [1] "Querying.............  Cytokine-cytokine receptor interaction   95 of 307 pathways"
## [1] "Querying.............  Viral protein interaction with cytokine and cytokine receptor   96 of 307 pathways"
## [1] "Querying.............  Chemokine signaling pathway   97 of 307 pathways"
## [1] "Querying.............  NF-kappa B signaling pathway   98 of 307 pathways"
## [1] "Querying.............  HIF-1 signaling pathway   99 of 307 pathways"
## [1] "Querying.............  FoxO signaling pathway   100 of 307 pathways"
## [1] "Querying.............  Phosphatidylinositol signaling system   101 of 307 pathways"
## [1] "Querying.............  Sphingolipid signaling pathway   102 of 307 pathways"
## [1] "Querying.............  Phospholipase D signaling pathway   103 of 307 pathways"
## [1] "Querying.............  Neuroactive ligand-receptor interaction   104 of 307 pathways"
## [1] "Querying.............  Cell cycle   105 of 307 pathways"
## [1] "Querying.............  Oocyte meiosis   106 of 307 pathways"
## [1] "Querying.............  p53 signaling pathway   107 of 307 pathways"
## [1] "Querying.............  Sulfur relay system   108 of 307 pathways"
## [1] "Querying.............  SNARE interactions in vesicular transport   109 of 307 pathways"
## [1] "Querying.............  Autophagy - other   110 of 307 pathways"
## [1] "Querying.............  Mitophagy - animal   111 of 307 pathways"
## [1] "Querying.............  Autophagy - animal   112 of 307 pathways"
## [1] "Querying.............  Protein processing in endoplasmic reticulum   113 of 307 pathways"
## [1] "Querying.............  Endocytosis   114 of 307 pathways"
## [1] "Querying.............  Phagosome   115 of 307 pathways"
## [1] "Querying.............  Peroxisome   116 of 307 pathways"
## [1] "Querying.............  mTOR signaling pathway   117 of 307 pathways"
## [1] "Querying.............  PI3K-Akt signaling pathway   118 of 307 pathways"
## [1] "Querying.............  AMPK signaling pathway   119 of 307 pathways"
## [1] "Querying.............  Apoptosis   120 of 307 pathways"
## [1] "Querying.............  Longevity regulating pathway   121 of 307 pathways"
## [1] "Querying.............  Longevity regulating pathway - multiple species   122 of 307 pathways"
## [1] "Querying.............  Apoptosis - multiple species   123 of 307 pathways"
## [1] "Querying.............  Ferroptosis   124 of 307 pathways"
## [1] "Querying.............  Necroptosis   125 of 307 pathways"
## [1] "Querying.............  Cellular senescence   126 of 307 pathways"
## [1] "Querying.............  Cardiac muscle contraction   127 of 307 pathways"
## [1] "Querying.............  Adrenergic signaling in cardiomyocytes   128 of 307 pathways"
## [1] "Querying.............  Vascular smooth muscle contraction   129 of 307 pathways"
## [1] "Querying.............  Wnt signaling pathway   130 of 307 pathways"
## [1] "Querying.............  Notch signaling pathway   131 of 307 pathways"
## [1] "Querying.............  Hedgehog signaling pathway   132 of 307 pathways"
## [1] "Querying.............  TGF-beta signaling pathway   133 of 307 pathways"
## [1] "Querying.............  Axon guidance   134 of 307 pathways"
## [1] "Querying.............  VEGF signaling pathway   135 of 307 pathways"
## [1] "Querying.............  Apelin signaling pathway   136 of 307 pathways"
## [1] "Querying.............  Osteoclast differentiation   137 of 307 pathways"
## [1] "Querying.............  Hippo signaling pathway   138 of 307 pathways"
## [1] "Querying.............  Hippo signaling pathway - multiple species   139 of 307 pathways"
## [1] "Querying.............  Focal adhesion   140 of 307 pathways"
## [1] "Querying.............  ECM-receptor interaction   141 of 307 pathways"
## [1] "Querying.............  Cell adhesion molecules (CAMs)   142 of 307 pathways"
## [1] "Querying.............  Adherens junction   143 of 307 pathways"
## [1] "Querying.............  Tight junction   144 of 307 pathways"
## [1] "Querying.............  Gap junction   145 of 307 pathways"
## [1] "Querying.............  Signaling pathways regulating pluripotency of stem cells   146 of 307 pathways"
## [1] "Querying.............  Complement and coagulation cascades   147 of 307 pathways"
## [1] "Querying.............  Platelet activation   148 of 307 pathways"
## [1] "Querying.............  Antigen processing and presentation   149 of 307 pathways"
## [1] "Querying.............  Renin-angiotensin system   150 of 307 pathways"
## [1] "Querying.............  Toll-like receptor signaling pathway   151 of 307 pathways"
## [1] "Querying.............  NOD-like receptor signaling pathway   152 of 307 pathways"
## [1] "Querying.............  RIG-I-like receptor signaling pathway   153 of 307 pathways"
## [1] "Querying.............  Cytosolic DNA-sensing pathway   154 of 307 pathways"
## [1] "Querying.............  C-type lectin receptor signaling pathway   155 of 307 pathways"
## [1] "Querying.............  JAK-STAT signaling pathway   156 of 307 pathways"
## [1] "Querying.............  Natural killer cell mediated cytotoxicity   157 of 307 pathways"
## [1] "Querying.............  IL-17 signaling pathway   158 of 307 pathways"
## [1] "Querying.............  Th1 and Th2 cell differentiation   159 of 307 pathways"
## [1] "Querying.............  Th17 cell differentiation   160 of 307 pathways"
## [1] "Querying.............  T cell receptor signaling pathway   161 of 307 pathways"
## [1] "Querying.............  B cell receptor signaling pathway   162 of 307 pathways"
## [1] "Querying.............  Fc epsilon RI signaling pathway   163 of 307 pathways"
## [1] "Querying.............  Fc gamma R-mediated phagocytosis   164 of 307 pathways"
## [1] "Querying.............  TNF signaling pathway   165 of 307 pathways"
## [1] "Querying.............  Leukocyte transendothelial migration   166 of 307 pathways"
## [1] "Querying.............  Intestinal immune network for IgA production   167 of 307 pathways"
## [1] "Querying.............  Circadian rhythm   168 of 307 pathways"
## [1] "Querying.............  Circadian entrainment   169 of 307 pathways"
## [1] "Querying.............  Thermogenesis   170 of 307 pathways"
## [1] "Querying.............  Long-term potentiation   171 of 307 pathways"
## [1] "Querying.............  Synaptic vesicle cycle   172 of 307 pathways"
## [1] "Querying.............  Neurotrophin signaling pathway   173 of 307 pathways"
## [1] "Querying.............  Retrograde endocannabinoid signaling   174 of 307 pathways"
## [1] "Querying.............  Glutamatergic synapse   175 of 307 pathways"
## [1] "Querying.............  Cholinergic synapse   176 of 307 pathways"
## [1] "Querying.............  Serotonergic synapse   177 of 307 pathways"
## [1] "Querying.............  GABAergic synapse   178 of 307 pathways"
## [1] "Querying.............  Dopaminergic synapse   179 of 307 pathways"
## [1] "Querying.............  Long-term depression   180 of 307 pathways"
## [1] "Querying.............  Olfactory transduction   181 of 307 pathways"
## [1] "Querying.............  Taste transduction   182 of 307 pathways"
## [1] "Querying.............  Phototransduction   183 of 307 pathways"
## [1] "Querying.............  Inflammatory mediator regulation of TRP channels   184 of 307 pathways"
## [1] "Querying.............  Regulation of actin cytoskeleton   185 of 307 pathways"
## [1] "Querying.............  Insulin signaling pathway   186 of 307 pathways"
## [1] "Querying.............  Insulin secretion   187 of 307 pathways"
## [1] "Querying.............  GnRH signaling pathway   188 of 307 pathways"
## [1] "Querying.............  Ovarian steroidogenesis   189 of 307 pathways"
## [1] "Querying.............  Progesterone-mediated oocyte maturation   190 of 307 pathways"
## [1] "Querying.............  Estrogen signaling pathway   191 of 307 pathways"
## [1] "Querying.............  Melanogenesis   192 of 307 pathways"
## [1] "Querying.............  Prolactin signaling pathway   193 of 307 pathways"
## [1] "Querying.............  Thyroid hormone synthesis   194 of 307 pathways"
## [1] "Querying.............  Thyroid hormone signaling pathway   195 of 307 pathways"
## [1] "Querying.............  Adipocytokine signaling pathway   196 of 307 pathways"
## [1] "Querying.............  Oxytocin signaling pathway   197 of 307 pathways"
## [1] "Querying.............  Glucagon signaling pathway   198 of 307 pathways"
## [1] "Querying.............  Regulation of lipolysis in adipocytes   199 of 307 pathways"
## [1] "Querying.............  Renin secretion   200 of 307 pathways"
## [1] "Querying.............  Aldosterone synthesis and secretion   201 of 307 pathways"
## [1] "Querying.............  Relaxin signaling pathway   202 of 307 pathways"
## [1] "Querying.............  Cortisol synthesis and secretion   203 of 307 pathways"
## [1] "Querying.............  Parathyroid hormone synthesis, secretion and action   204 of 307 pathways"
## [1] "Querying.............  GnRH secretion   205 of 307 pathways"
## [1] "Querying.............  Type II diabetes mellitus   206 of 307 pathways"
## [1] "Querying.............  Insulin resistance   207 of 307 pathways"
## [1] "Querying.............  Non-alcoholic fatty liver disease (NAFLD)   208 of 307 pathways"
## [1] "Querying.............  AGE-RAGE signaling pathway in diabetic complications   209 of 307 pathways"
## [1] "Querying.............  Cushing syndrome   210 of 307 pathways"
## [1] "Querying.............  Growth hormone synthesis, secretion and action   211 of 307 pathways"
## [1] "Querying.............  Type I diabetes mellitus   212 of 307 pathways"
## [1] "Querying.............  Maturity onset diabetes of the young   213 of 307 pathways"
## [1] "Querying.............  Aldosterone-regulated sodium reabsorption   214 of 307 pathways"
## [1] "Querying.............  Endocrine and other factor-regulated calcium reabsorption   215 of 307 pathways"
## [1] "Querying.............  Vasopressin-regulated water reabsorption   216 of 307 pathways"
## [1] "Querying.............  Proximal tubule bicarbonate reclamation   217 of 307 pathways"
## [1] "Querying.............  Salivary secretion   218 of 307 pathways"
## [1] "Querying.............  Gastric acid secretion   219 of 307 pathways"
## [1] "Querying.............  Pancreatic secretion   220 of 307 pathways"
## [1] "Querying.............  Carbohydrate digestion and absorption   221 of 307 pathways"
## [1] "Querying.............  Fat digestion and absorption   222 of 307 pathways"
## [1] "Querying.............  Bile secretion   223 of 307 pathways"
## [1] "Querying.............  Vitamin digestion and absorption   224 of 307 pathways"
## [1] "Querying.............  Mineral absorption   225 of 307 pathways"
## [1] "Querying.............  Cholesterol metabolism   226 of 307 pathways"
## [1] "Querying.............  Alzheimer disease   227 of 307 pathways"
## [1] "Querying.............  Parkinson disease   228 of 307 pathways"
## [1] "Querying.............  Amyotrophic lateral sclerosis (ALS)   229 of 307 pathways"
## [1] "Querying.............  Huntington disease   230 of 307 pathways"
## [1] "Querying.............  Spinocerebellar ataxia   231 of 307 pathways"
## [1] "Querying.............  Prion diseases   232 of 307 pathways"
## [1] "Querying.............  Cocaine addiction   233 of 307 pathways"
## [1] "Querying.............  Amphetamine addiction   234 of 307 pathways"
## [1] "Querying.............  Morphine addiction   235 of 307 pathways"
## [1] "Querying.............  Alcoholism   236 of 307 pathways"
## [1] "Querying.............  Bacterial invasion of epithelial cells   237 of 307 pathways"
## [1] "Querying.............  Vibrio cholerae infection   238 of 307 pathways"
## [1] "Querying.............  Epithelial cell signaling in Helicobacter pylori infection   239 of 307 pathways"
## [1] "Querying.............  Pathogenic Escherichia coli infection   240 of 307 pathways"
## [1] "Querying.............  Shigellosis   241 of 307 pathways"
## [1] "Querying.............  Salmonella infection   242 of 307 pathways"
## [1] "Querying.............  Pertussis   243 of 307 pathways"
## [1] "Querying.............  Legionellosis   244 of 307 pathways"
## [1] "Querying.............  Yersinia infection   245 of 307 pathways"
## [1] "Querying.............  Leishmaniasis   246 of 307 pathways"
## [1] "Querying.............  Chagas disease (American trypanosomiasis)   247 of 307 pathways"
## [1] "Querying.............  African trypanosomiasis   248 of 307 pathways"
## [1] "Querying.............  Malaria   249 of 307 pathways"
## [1] "Querying.............  Toxoplasmosis   250 of 307 pathways"
## [1] "Querying.............  Amoebiasis   251 of 307 pathways"
## [1] "Querying.............  Staphylococcus aureus infection   252 of 307 pathways"
## [1] "Querying.............  Tuberculosis   253 of 307 pathways"
## [1] "Querying.............  Hepatitis C   254 of 307 pathways"
## [1] "Querying.............  Hepatitis B   255 of 307 pathways"
## [1] "Querying.............  Measles   256 of 307 pathways"
## [1] "Querying.............  Human cytomegalovirus infection   257 of 307 pathways"
## [1] "Querying.............  Influenza A   258 of 307 pathways"
## [1] "Querying.............  Human papillomavirus infection   259 of 307 pathways"
## [1] "Querying.............  Human T-cell leukemia virus 1 infection   260 of 307 pathways"
## [1] "Querying.............  Kaposi sarcoma-associated herpesvirus infection   261 of 307 pathways"
## [1] "Querying.............  Herpes simplex virus 1 infection   262 of 307 pathways"
## [1] "Querying.............  Epstein-Barr virus infection   263 of 307 pathways"
## [1] "Querying.............  Human immunodeficiency virus 1 infection   264 of 307 pathways"
## [1] "Querying.............  Pathways in cancer   265 of 307 pathways"
## [1] "Querying.............  Transcriptional misregulation in cancer   266 of 307 pathways"
## [1] "Querying.............  Viral carcinogenesis   267 of 307 pathways"
## [1] "Querying.............  Chemical carcinogenesis   268 of 307 pathways"
## [1] "Querying.............  Proteoglycans in cancer   269 of 307 pathways"
## [1] "Querying.............  MicroRNAs in cancer   270 of 307 pathways"
## [1] "Querying.............  Colorectal cancer   271 of 307 pathways"
## [1] "Querying.............  Renal cell carcinoma   272 of 307 pathways"
## [1] "Querying.............  Pancreatic cancer   273 of 307 pathways"
## [1] "Querying.............  Endometrial cancer   274 of 307 pathways"
## [1] "Querying.............  Glioma   275 of 307 pathways"
## [1] "Querying.............  Prostate cancer   276 of 307 pathways"
## [1] "Querying.............  Thyroid cancer   277 of 307 pathways"
## [1] "Querying.............  Basal cell carcinoma   278 of 307 pathways"
## [1] "Querying.............  Melanoma   279 of 307 pathways"
## [1] "Querying.............  Bladder cancer   280 of 307 pathways"
## [1] "Querying.............  Chronic myeloid leukemia   281 of 307 pathways"
## [1] "Querying.............  Acute myeloid leukemia   282 of 307 pathways"
## [1] "Querying.............  Small cell lung cancer   283 of 307 pathways"
## [1] "Querying.............  Non-small cell lung cancer   284 of 307 pathways"
## [1] "Querying.............  Breast cancer   285 of 307 pathways"
## [1] "Querying.............  Hepatocellular carcinoma   286 of 307 pathways"
## [1] "Querying.............  Gastric cancer   287 of 307 pathways"
## [1] "Querying.............  Central carbon metabolism in cancer   288 of 307 pathways"
## [1] "Querying.............  Choline metabolism in cancer   289 of 307 pathways"
## [1] "Querying.............  PD-L1 expression and PD-1 checkpoint pathway in cancer   290 of 307 pathways"
## [1] "Querying.............  Asthma   291 of 307 pathways"
## [1] "Querying.............  Autoimmune thyroid disease   292 of 307 pathways"
## [1] "Querying.............  Inflammatory bowel disease (IBD)   293 of 307 pathways"
## [1] "Querying.............  Systemic lupus erythematosus   294 of 307 pathways"
## [1] "Querying.............  Rheumatoid arthritis   295 of 307 pathways"
## [1] "Querying.............  Allograft rejection   296 of 307 pathways"
## [1] "Querying.............  Graft-versus-host disease   297 of 307 pathways"
## [1] "Querying.............  Hypertrophic cardiomyopathy (HCM)   298 of 307 pathways"
## [1] "Querying.............  Arrhythmogenic right ventricular cardiomyopathy (ARVC)   299 of 307 pathways"
## [1] "Querying.............  Dilated cardiomyopathy (DCM)   300 of 307 pathways"
## [1] "Querying.............  Viral myocarditis   301 of 307 pathways"
## [1] "Querying.............  Fluid shear stress and atherosclerosis   302 of 307 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine biosynthesis   303 of 307 pathways"
## [1] "Querying.............  D-Arginine and D-ornithine metabolism   304 of 307 pathways"
## [1] "Querying.............  Neomycin, kanamycin and gentamicin biosynthesis   305 of 307 pathways"
## [1] "Querying.............  Protein digestion and absorption   306 of 307 pathways"
## [1] "Querying.............  Nicotine addiction   307 of 307 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 4.0.0 (2020-04-24)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 18.04.4 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.11-bioc/R/lib/libRblas.so
## LAPACK: /home/biocbuild/bbs-3.11-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_1.6.5         org.Hs.eg.db_3.10.0 
##  [4] graphite_1.34.0      StarBioTrek_1.14.0   miRNAtap_1.22.0     
##  [7] AnnotationDbi_1.50.0 IRanges_2.22.0       S4Vectors_0.26.0    
## [10] Biobase_2.48.0       BiocGenerics_0.34.0  BiocStyle_2.16.0    
## 
## loaded via a namespace (and not attached):
##   [1] rappdirs_0.3.1         lavaan_0.6-5           tidyr_1.0.2           
##   [4] ggplot2_3.3.0          acepack_1.4.1          bit64_0.9-7           
##   [7] knitr_1.28             data.table_1.12.8      rpart_4.1-15          
##  [10] KEGGREST_1.28.0        RCurl_1.98-1.2         callr_3.4.3           
##  [13] cowplot_1.0.0          usethis_1.6.0          RSQLite_2.2.0         
##  [16] europepmc_0.3          chron_2.3-55           bit_1.1-15.2          
##  [19] enrichplot_1.8.0       xml2_1.3.2             ggsci_2.9             
##  [22] assertthat_0.2.1       d3Network_0.5.2.1      viridis_0.5.1         
##  [25] xfun_0.13              hms_0.5.3              evaluate_0.14         
##  [28] fansi_0.4.1            progress_1.2.2         caTools_1.18.0        
##  [31] dendextend_1.13.4      dbplyr_1.4.3           Rgraphviz_2.32.0      
##  [34] igraph_1.2.5           DBI_1.1.0              htmlwidgets_1.5.1     
##  [37] purrr_0.3.4            ellipsis_0.3.0         dplyr_0.8.5           
##  [40] ggpubr_0.2.5           backports_1.1.6        bookdown_0.18         
##  [43] pbivnorm_0.6.0         MLmetrics_1.1.1        annotate_1.66.0       
##  [46] MAGeCKFlute_1.8.0      biomaRt_2.44.0         vctrs_0.2.4           
##  [49] remotes_2.1.1          ROCR_1.0-7             abind_1.4-5           
##  [52] pathview_1.28.0        withr_2.2.0            ggforce_0.3.1         
##  [55] triebeard_0.3.0        checkmate_2.0.0        fdrtool_1.2.15        
##  [58] prettyunits_1.1.1      mnormt_1.5-6           cluster_2.1.0         
##  [61] DOSE_3.14.0            crayon_1.3.4           genefilter_1.70.0     
##  [64] edgeR_3.30.0           pkgconfig_2.0.3        tweenr_1.0.1          
##  [67] nlme_3.1-147           pkgload_1.0.2          nnet_7.3-14           
##  [70] devtools_2.3.0         rlang_0.4.5            lifecycle_0.2.0       
##  [73] downloader_0.4         BiocFileCache_1.12.0   rprojroot_1.3-2       
##  [76] polyclip_1.10-0        matrixStats_0.56.0     graph_1.66.0          
##  [79] Matrix_1.2-18          urltools_1.7.3         base64enc_0.1-3       
##  [82] whisker_0.4            ggridges_0.5.2         processx_3.4.2        
##  [85] pheatmap_1.0.12        rjson_0.2.20           viridisLite_0.3.0     
##  [88] bitops_1.0-6           KernSmooth_2.23-17     visNetwork_2.0.9      
##  [91] Biostrings_2.56.0      blob_1.2.1             stringr_1.4.0         
##  [94] qvalue_2.20.0          jpeg_0.1-8.1           gridGraphics_0.5-0    
##  [97] ggsignif_0.6.0         scales_1.1.0           memoise_1.1.0         
## [100] magrittr_1.5           plyr_1.8.6             gplots_3.0.3          
## [103] gdata_2.18.0           zlibbioc_1.34.0        compiler_4.0.0        
## [106] scatterpie_0.1.4       RColorBrewer_1.1-2     KEGGgraph_1.48.0      
## [109] miRNAtap.db_0.99.10    cli_2.0.2              XVector_0.28.0        
## [112] pbapply_1.4-2          ps_1.3.2               htmlTable_1.13.3      
## [115] Formula_1.2-3          MASS_7.3-51.6          mgcv_1.8-31           
## [118] tidyselect_1.0.0       stringi_1.4.6          highr_0.8             
## [121] yaml_2.2.1             GOSemSim_2.14.0        askpass_1.1           
## [124] locfit_1.5-9.4         latticeExtra_0.6-29    ggrepel_0.8.2         
## [127] fastmatch_1.1-0        tools_4.0.0            rstudioapi_0.11       
## [130] foreign_0.8-79         gridExtra_2.3          farver_2.0.3          
## [133] BDgraph_2.62           ggraph_2.0.2           digest_0.6.25         
## [136] rvcheck_0.1.8          BiocManager_1.30.10    proto_1.0.0           
## [139] networkD3_0.4          Rcpp_1.0.4.6           httr_1.4.1            
## [142] psych_1.9.12.31        colorspace_1.4-1       XML_3.99-0.3          
## [145] fs_1.4.1               splines_4.0.0          graphlayouts_0.7.0    
## [148] ggplotify_0.0.5        sessioninfo_1.1.1      xtable_1.8-4          
## [151] jsonlite_1.6.1         SpidermiR_1.18.0       tidygraph_1.1.2       
## [154] corpcor_1.6.9          glasso_1.11            testthat_2.3.2        
## [157] R6_2.4.1               Hmisc_4.4-0            gsubfn_0.7            
## [160] pillar_1.4.3           htmltools_0.4.0        glue_1.4.0            
## [163] clusterProfiler_3.16.0 BiocParallel_1.22.0    class_7.3-17          
## [166] fgsea_1.14.0           pkgbuild_1.0.7         lattice_0.20-41       
## [169] tibble_3.0.1           sva_3.36.0             sqldf_0.4-11          
## [172] huge_1.3.4.1           curl_4.3               gtools_3.8.2          
## [175] magick_2.3             GO.db_3.10.0           openssl_1.4.1         
## [178] survival_3.1-12        limma_3.44.0           rmarkdown_2.1         
## [181] desc_1.2.0             munsell_0.5.0          e1071_1.7-3           
## [184] DO.db_2.9              reshape2_1.4.4         gtable_0.3.0          
## [187] msigdbr_7.0.1

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.”