Contents

Introduction

Motivation: New technologies have made possible to identify marker gene signatures. However, gene expression-based signatures present some limitations because they do not consider metabolic role of the genes and are affected by genetic heterogeneity across patient cohorts. Considering the activity of entire pathways rather than the expression levels of individual genes can be a way to exceed these limits (Cancer Genome Atlas Research Network and others 2012). This tool StarBioTrek presents some methodologies to measure pathway activity and cross-talk among pathways integrating also the information of network and TCGA data. New measures are under development.

Installation

To install use the code below.

Get data: Get pathway and network data

SELECT_path_species: Select the pathway database and species of interest

The user can select the pathway database and species of interest using some functions implemented in graphite (Sales G, et al. 2012)


Table 1: List of patwhay databases and species
species database
athaliana kegg
athaliana pathbank
athaliana wikipathways
btaurus kegg
btaurus pathbank
btaurus reactome
btaurus wikipathways
celegans kegg
celegans pathbank
celegans reactome
celegans wikipathways
cfamiliaris kegg
cfamiliaris reactome
cfamiliaris wikipathways
dmelanogaster kegg
dmelanogaster pathbank
dmelanogaster reactome
dmelanogaster wikipathways
drerio kegg
drerio reactome
drerio wikipathways
ecoli kegg
ecoli pathbank
ecoli wikipathways
ggallus kegg
ggallus reactome
ggallus wikipathways
hsapiens kegg
hsapiens panther
hsapiens pathbank
hsapiens pharmgkb
hsapiens reactome
hsapiens smpdb
hsapiens wikipathways
mmusculus kegg
mmusculus pathbank
mmusculus reactome
mmusculus wikipathways
rnorvegicus kegg
rnorvegicus pathbank
rnorvegicus reactome
rnorvegicus wikipathways
scerevisiae kegg
scerevisiae pathbank
scerevisiae reactome
scerevisiae wikipathways
sscrofa kegg
sscrofa reactome
sscrofa wikipathways
xlaevis kegg

GetData: Searching pathway data for download

The user can easily search pathways data and their genes using the GetData function. It can download pathways from several databases and species using the following parameters:

## [1] "Querying.............  Glycolysis / Gluconeogenesis   1 of 323 pathways"
## [1] "Querying.............  Citrate cycle (TCA cycle)   2 of 323 pathways"
## [1] "Querying.............  Pentose phosphate pathway   3 of 323 pathways"
## [1] "Querying.............  Pentose and glucuronate interconversions   4 of 323 pathways"
## [1] "Querying.............  Fructose and mannose metabolism   5 of 323 pathways"
## [1] "Querying.............  Galactose metabolism   6 of 323 pathways"
## [1] "Querying.............  Ascorbate and aldarate metabolism   7 of 323 pathways"
## [1] "Querying.............  Fatty acid biosynthesis   8 of 323 pathways"
## [1] "Querying.............  Fatty acid elongation   9 of 323 pathways"
## [1] "Querying.............  Fatty acid degradation   10 of 323 pathways"
## [1] "Querying.............  Steroid biosynthesis   11 of 323 pathways"
## [1] "Querying.............  Primary bile acid biosynthesis   12 of 323 pathways"
## [1] "Querying.............  Ubiquinone and other terpenoid-quinone biosynthesis   13 of 323 pathways"
## [1] "Querying.............  Steroid hormone biosynthesis   14 of 323 pathways"
## [1] "Querying.............  Oxidative phosphorylation   15 of 323 pathways"
## [1] "Querying.............  Arginine biosynthesis   16 of 323 pathways"
## [1] "Querying.............  Purine metabolism   17 of 323 pathways"
## [1] "Querying.............  Caffeine metabolism   18 of 323 pathways"
## [1] "Querying.............  Pyrimidine metabolism   19 of 323 pathways"
## [1] "Querying.............  Alanine, aspartate and glutamate metabolism   20 of 323 pathways"
## [1] "Querying.............  Glycine, serine and threonine metabolism   21 of 323 pathways"
## [1] "Querying.............  Cysteine and methionine metabolism   22 of 323 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine degradation   23 of 323 pathways"
## [1] "Querying.............  Lysine degradation   24 of 323 pathways"
## [1] "Querying.............  Arginine and proline metabolism   25 of 323 pathways"
## [1] "Querying.............  Histidine metabolism   26 of 323 pathways"
## [1] "Querying.............  Tyrosine metabolism   27 of 323 pathways"
## [1] "Querying.............  Phenylalanine metabolism   28 of 323 pathways"
## [1] "Querying.............  Tryptophan metabolism   29 of 323 pathways"
## [1] "Querying.............  Phenylalanine, tyrosine and tryptophan biosynthesis   30 of 323 pathways"
## [1] "Querying.............  beta-Alanine metabolism   31 of 323 pathways"
## [1] "Querying.............  Taurine and hypotaurine metabolism   32 of 323 pathways"
## [1] "Querying.............  Phosphonate and phosphinate metabolism   33 of 323 pathways"
## [1] "Querying.............  Selenocompound metabolism   34 of 323 pathways"
## [1] "Querying.............  D-Amino acid metabolism   35 of 323 pathways"
## [1] "Querying.............  Glutathione metabolism   36 of 323 pathways"
## [1] "Querying.............  Starch and sucrose metabolism   37 of 323 pathways"
## [1] "Querying.............  N-Glycan biosynthesis   38 of 323 pathways"
## [1] "Querying.............  Mucin type O-glycan biosynthesis   39 of 323 pathways"
## [1] "Querying.............  Various types of N-glycan biosynthesis   40 of 323 pathways"
## [1] "Querying.............  Mannose type O-glycan biosynthesis   41 of 323 pathways"
## [1] "Querying.............  Amino sugar and nucleotide sugar metabolism   42 of 323 pathways"
## [1] "Querying.............  Glycosaminoglycan degradation   43 of 323 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate   44 of 323 pathways"
## [1] "Querying.............  Glycosaminoglycan biosynthesis - heparan sulfate / heparin   45 of 323 pathways"
## [1] "Querying.............  Glycerolipid metabolism   46 of 323 pathways"
## [1] "Querying.............  Inositol phosphate metabolism   47 of 323 pathways"
## [1] "Querying.............  Glycosylphosphatidylinositol (GPI)-anchor biosynthesis   48 of 323 pathways"
## [1] "Querying.............  Glycerophospholipid metabolism   49 of 323 pathways"
## [1] "Querying.............  Ether lipid metabolism   50 of 323 pathways"
## [1] "Querying.............  Arachidonic acid metabolism   51 of 323 pathways"
## [1] "Querying.............  Linoleic acid metabolism   52 of 323 pathways"
## [1] "Querying.............  alpha-Linolenic acid metabolism   53 of 323 pathways"
## [1] "Querying.............  Sphingolipid metabolism   54 of 323 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - lacto and neolacto series   55 of 323 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - globo and isoglobo series   56 of 323 pathways"
## [1] "Querying.............  Glycosphingolipid biosynthesis - ganglio series   57 of 323 pathways"
## [1] "Querying.............  Pyruvate metabolism   58 of 323 pathways"
## [1] "Querying.............  Glyoxylate and dicarboxylate metabolism   59 of 323 pathways"
## [1] "Querying.............  Propanoate metabolism   60 of 323 pathways"
## [1] "Querying.............  Butanoate metabolism   61 of 323 pathways"
## [1] "Querying.............  One carbon pool by folate   62 of 323 pathways"
## [1] "Querying.............  Thiamine metabolism   63 of 323 pathways"
## [1] "Querying.............  Riboflavin metabolism   64 of 323 pathways"
## [1] "Querying.............  Vitamin B6 metabolism   65 of 323 pathways"
## [1] "Querying.............  Nicotinate and nicotinamide metabolism   66 of 323 pathways"
## [1] "Querying.............  Pantothenate and CoA biosynthesis   67 of 323 pathways"
## [1] "Querying.............  Biotin metabolism   68 of 323 pathways"
## [1] "Querying.............  Lipoic acid metabolism   69 of 323 pathways"
## [1] "Querying.............  Folate biosynthesis   70 of 323 pathways"
## [1] "Querying.............  Retinol metabolism   71 of 323 pathways"
## [1] "Querying.............  Porphyrin and chlorophyll metabolism   72 of 323 pathways"
## [1] "Querying.............  Terpenoid backbone biosynthesis   73 of 323 pathways"
## [1] "Querying.............  Nitrogen metabolism   74 of 323 pathways"
## [1] "Querying.............  Sulfur metabolism   75 of 323 pathways"
## [1] "Querying.............  Aminoacyl-tRNA biosynthesis   76 of 323 pathways"
## [1] "Querying.............  Metabolism of xenobiotics by cytochrome P450   77 of 323 pathways"
## [1] "Querying.............  Drug metabolism - cytochrome P450   78 of 323 pathways"
## [1] "Querying.............  Drug metabolism - other enzymes   79 of 323 pathways"
## [1] "Querying.............  Biosynthesis of unsaturated fatty acids   80 of 323 pathways"
## [1] "Querying.............  Metabolic pathways   81 of 323 pathways"
## [1] "Querying.............  Carbon metabolism   82 of 323 pathways"
## [1] "Querying.............  2-Oxocarboxylic acid metabolism   83 of 323 pathways"
## [1] "Querying.............  Fatty acid metabolism   84 of 323 pathways"
## [1] "Querying.............  Biosynthesis of amino acids   85 of 323 pathways"
## [1] "Querying.............  Biosynthesis of cofactors   86 of 323 pathways"
## [1] "Querying.............  Biosynthesis of nucleotide sugars   87 of 323 pathways"
## [1] "Querying.............  EGFR tyrosine kinase inhibitor resistance   88 of 323 pathways"
## [1] "Querying.............  Endocrine resistance   89 of 323 pathways"
## [1] "Querying.............  Antifolate resistance   90 of 323 pathways"
## [1] "Querying.............  Platinum drug resistance   91 of 323 pathways"
## [1] "Querying.............  mRNA surveillance pathway   92 of 323 pathways"
## [1] "Querying.............  RNA degradation   93 of 323 pathways"
## [1] "Querying.............  PPAR signaling pathway   94 of 323 pathways"
## [1] "Querying.............  Homologous recombination   95 of 323 pathways"
## [1] "Querying.............  Fanconi anemia pathway   96 of 323 pathways"
## [1] "Querying.............  MAPK signaling pathway   97 of 323 pathways"
## [1] "Querying.............  ErbB signaling pathway   98 of 323 pathways"
## [1] "Querying.............  Ras signaling pathway   99 of 323 pathways"
## [1] "Querying.............  Rap1 signaling pathway   100 of 323 pathways"
## [1] "Querying.............  Calcium signaling pathway   101 of 323 pathways"
## [1] "Querying.............  cGMP-PKG signaling pathway   102 of 323 pathways"
## [1] "Querying.............  cAMP signaling pathway   103 of 323 pathways"
## [1] "Querying.............  Cytokine-cytokine receptor interaction   104 of 323 pathways"
## [1] "Querying.............  Viral protein interaction with cytokine and cytokine receptor   105 of 323 pathways"
## [1] "Querying.............  Chemokine signaling pathway   106 of 323 pathways"
## [1] "Querying.............  NF-kappa B signaling pathway   107 of 323 pathways"
## [1] "Querying.............  HIF-1 signaling pathway   108 of 323 pathways"
## [1] "Querying.............  FoxO signaling pathway   109 of 323 pathways"
## [1] "Querying.............  Phosphatidylinositol signaling system   110 of 323 pathways"
## [1] "Querying.............  Sphingolipid signaling pathway   111 of 323 pathways"
## [1] "Querying.............  Phospholipase D signaling pathway   112 of 323 pathways"
## [1] "Querying.............  Neuroactive ligand-receptor interaction   113 of 323 pathways"
## [1] "Querying.............  Cell cycle   114 of 323 pathways"
## [1] "Querying.............  Oocyte meiosis   115 of 323 pathways"
## [1] "Querying.............  p53 signaling pathway   116 of 323 pathways"
## [1] "Querying.............  Sulfur relay system   117 of 323 pathways"
## [1] "Querying.............  SNARE interactions in vesicular transport   118 of 323 pathways"
## [1] "Querying.............  Autophagy - other   119 of 323 pathways"
## [1] "Querying.............  Mitophagy - animal   120 of 323 pathways"
## [1] "Querying.............  Autophagy - animal   121 of 323 pathways"
## [1] "Querying.............  Protein processing in endoplasmic reticulum   122 of 323 pathways"
## [1] "Querying.............  Endocytosis   123 of 323 pathways"
## [1] "Querying.............  Phagosome   124 of 323 pathways"
## [1] "Querying.............  Peroxisome   125 of 323 pathways"
## [1] "Querying.............  mTOR signaling pathway   126 of 323 pathways"
## [1] "Querying.............  PI3K-Akt signaling pathway   127 of 323 pathways"
## [1] "Querying.............  AMPK signaling pathway   128 of 323 pathways"
## [1] "Querying.............  Apoptosis   129 of 323 pathways"
## [1] "Querying.............  Longevity regulating pathway   130 of 323 pathways"
## [1] "Querying.............  Longevity regulating pathway - multiple species   131 of 323 pathways"
## [1] "Querying.............  Apoptosis - multiple species   132 of 323 pathways"
## [1] "Querying.............  Ferroptosis   133 of 323 pathways"
## [1] "Querying.............  Necroptosis   134 of 323 pathways"
## [1] "Querying.............  Cellular senescence   135 of 323 pathways"
## [1] "Querying.............  Cardiac muscle contraction   136 of 323 pathways"
## [1] "Querying.............  Adrenergic signaling in cardiomyocytes   137 of 323 pathways"
## [1] "Querying.............  Vascular smooth muscle contraction   138 of 323 pathways"
## [1] "Querying.............  Wnt signaling pathway   139 of 323 pathways"
## [1] "Querying.............  Notch signaling pathway   140 of 323 pathways"
## [1] "Querying.............  Hedgehog signaling pathway   141 of 323 pathways"
## [1] "Querying.............  TGF-beta signaling pathway   142 of 323 pathways"
## [1] "Querying.............  Axon guidance   143 of 323 pathways"
## [1] "Querying.............  VEGF signaling pathway   144 of 323 pathways"
## [1] "Querying.............  Apelin signaling pathway   145 of 323 pathways"
## [1] "Querying.............  Osteoclast differentiation   146 of 323 pathways"
## [1] "Querying.............  Hippo signaling pathway   147 of 323 pathways"
## [1] "Querying.............  Hippo signaling pathway - multiple species   148 of 323 pathways"
## [1] "Querying.............  Focal adhesion   149 of 323 pathways"
## [1] "Querying.............  ECM-receptor interaction   150 of 323 pathways"
## [1] "Querying.............  Cell adhesion molecules   151 of 323 pathways"
## [1] "Querying.............  Adherens junction   152 of 323 pathways"
## [1] "Querying.............  Tight junction   153 of 323 pathways"
## [1] "Querying.............  Gap junction   154 of 323 pathways"
## [1] "Querying.............  Signaling pathways regulating pluripotency of stem cells   155 of 323 pathways"
## [1] "Querying.............  Complement and coagulation cascades   156 of 323 pathways"
## [1] "Querying.............  Platelet activation   157 of 323 pathways"
## [1] "Querying.............  Antigen processing and presentation   158 of 323 pathways"
## [1] "Querying.............  Neutrophil extracellular trap formation   159 of 323 pathways"
## [1] "Querying.............  Renin-angiotensin system   160 of 323 pathways"
## [1] "Querying.............  Toll-like receptor signaling pathway   161 of 323 pathways"
## [1] "Querying.............  NOD-like receptor signaling pathway   162 of 323 pathways"
## [1] "Querying.............  RIG-I-like receptor signaling pathway   163 of 323 pathways"
## [1] "Querying.............  Cytosolic DNA-sensing pathway   164 of 323 pathways"
## [1] "Querying.............  C-type lectin receptor signaling pathway   165 of 323 pathways"
## [1] "Querying.............  JAK-STAT signaling pathway   166 of 323 pathways"
## [1] "Querying.............  Natural killer cell mediated cytotoxicity   167 of 323 pathways"
## [1] "Querying.............  IL-17 signaling pathway   168 of 323 pathways"
## [1] "Querying.............  Th1 and Th2 cell differentiation   169 of 323 pathways"
## [1] "Querying.............  Th17 cell differentiation   170 of 323 pathways"
## [1] "Querying.............  T cell receptor signaling pathway   171 of 323 pathways"
## [1] "Querying.............  B cell receptor signaling pathway   172 of 323 pathways"
## [1] "Querying.............  Fc epsilon RI signaling pathway   173 of 323 pathways"
## [1] "Querying.............  Fc gamma R-mediated phagocytosis   174 of 323 pathways"
## [1] "Querying.............  TNF signaling pathway   175 of 323 pathways"
## [1] "Querying.............  Leukocyte transendothelial migration   176 of 323 pathways"
## [1] "Querying.............  Intestinal immune network for IgA production   177 of 323 pathways"
## [1] "Querying.............  Circadian rhythm   178 of 323 pathways"
## [1] "Querying.............  Circadian entrainment   179 of 323 pathways"
## [1] "Querying.............  Thermogenesis   180 of 323 pathways"
## [1] "Querying.............  Long-term potentiation   181 of 323 pathways"
## [1] "Querying.............  Synaptic vesicle cycle   182 of 323 pathways"
## [1] "Querying.............  Neurotrophin signaling pathway   183 of 323 pathways"
## [1] "Querying.............  Retrograde endocannabinoid signaling   184 of 323 pathways"
## [1] "Querying.............  Glutamatergic synapse   185 of 323 pathways"
## [1] "Querying.............  Cholinergic synapse   186 of 323 pathways"
## [1] "Querying.............  Serotonergic synapse   187 of 323 pathways"
## [1] "Querying.............  GABAergic synapse   188 of 323 pathways"
## [1] "Querying.............  Dopaminergic synapse   189 of 323 pathways"
## [1] "Querying.............  Long-term depression   190 of 323 pathways"
## [1] "Querying.............  Olfactory transduction   191 of 323 pathways"
## [1] "Querying.............  Taste transduction   192 of 323 pathways"
## [1] "Querying.............  Phototransduction   193 of 323 pathways"
## [1] "Querying.............  Inflammatory mediator regulation of TRP channels   194 of 323 pathways"
## [1] "Querying.............  Regulation of actin cytoskeleton   195 of 323 pathways"
## [1] "Querying.............  Insulin signaling pathway   196 of 323 pathways"
## [1] "Querying.............  Insulin secretion   197 of 323 pathways"
## [1] "Querying.............  GnRH signaling pathway   198 of 323 pathways"
## [1] "Querying.............  Ovarian steroidogenesis   199 of 323 pathways"
## [1] "Querying.............  Progesterone-mediated oocyte maturation   200 of 323 pathways"
## [1] "Querying.............  Estrogen signaling pathway   201 of 323 pathways"
## [1] "Querying.............  Melanogenesis   202 of 323 pathways"
## [1] "Querying.............  Prolactin signaling pathway   203 of 323 pathways"
## [1] "Querying.............  Thyroid hormone synthesis   204 of 323 pathways"
## [1] "Querying.............  Thyroid hormone signaling pathway   205 of 323 pathways"
## [1] "Querying.............  Adipocytokine signaling pathway   206 of 323 pathways"
## [1] "Querying.............  Oxytocin signaling pathway   207 of 323 pathways"
## [1] "Querying.............  Glucagon signaling pathway   208 of 323 pathways"
## [1] "Querying.............  Regulation of lipolysis in adipocytes   209 of 323 pathways"
## [1] "Querying.............  Renin secretion   210 of 323 pathways"
## [1] "Querying.............  Aldosterone synthesis and secretion   211 of 323 pathways"
## [1] "Querying.............  Relaxin signaling pathway   212 of 323 pathways"
## [1] "Querying.............  Cortisol synthesis and secretion   213 of 323 pathways"
## [1] "Querying.............  Parathyroid hormone synthesis, secretion and action   214 of 323 pathways"
## [1] "Querying.............  GnRH secretion   215 of 323 pathways"
## [1] "Querying.............  Type II diabetes mellitus   216 of 323 pathways"
## [1] "Querying.............  Insulin resistance   217 of 323 pathways"
## [1] "Querying.............  Non-alcoholic fatty liver disease   218 of 323 pathways"
## [1] "Querying.............  AGE-RAGE signaling pathway in diabetic complications   219 of 323 pathways"
## [1] "Querying.............  Cushing syndrome   220 of 323 pathways"
## [1] "Querying.............  Growth hormone synthesis, secretion and action   221 of 323 pathways"
## [1] "Querying.............  Alcoholic liver disease   222 of 323 pathways"
## [1] "Querying.............  Type I diabetes mellitus   223 of 323 pathways"
## [1] "Querying.............  Maturity onset diabetes of the young   224 of 323 pathways"
## [1] "Querying.............  Aldosterone-regulated sodium reabsorption   225 of 323 pathways"
## [1] "Querying.............  Endocrine and other factor-regulated calcium reabsorption   226 of 323 pathways"
## [1] "Querying.............  Vasopressin-regulated water reabsorption   227 of 323 pathways"
## [1] "Querying.............  Proximal tubule bicarbonate reclamation   228 of 323 pathways"
## [1] "Querying.............  Salivary secretion   229 of 323 pathways"
## [1] "Querying.............  Gastric acid secretion   230 of 323 pathways"
## [1] "Querying.............  Pancreatic secretion   231 of 323 pathways"
## [1] "Querying.............  Carbohydrate digestion and absorption   232 of 323 pathways"
## [1] "Querying.............  Fat digestion and absorption   233 of 323 pathways"
## [1] "Querying.............  Bile secretion   234 of 323 pathways"
## [1] "Querying.............  Vitamin digestion and absorption   235 of 323 pathways"
## [1] "Querying.............  Mineral absorption   236 of 323 pathways"
## [1] "Querying.............  Cholesterol metabolism   237 of 323 pathways"
## [1] "Querying.............  Alzheimer disease   238 of 323 pathways"
## [1] "Querying.............  Parkinson disease   239 of 323 pathways"
## [1] "Querying.............  Amyotrophic lateral sclerosis   240 of 323 pathways"
## [1] "Querying.............  Huntington disease   241 of 323 pathways"
## [1] "Querying.............  Spinocerebellar ataxia   242 of 323 pathways"
## [1] "Querying.............  Prion disease   243 of 323 pathways"
## [1] "Querying.............  Pathways of neurodegeneration - multiple diseases   244 of 323 pathways"
## [1] "Querying.............  Cocaine addiction   245 of 323 pathways"
## [1] "Querying.............  Amphetamine addiction   246 of 323 pathways"
## [1] "Querying.............  Morphine addiction   247 of 323 pathways"
## [1] "Querying.............  Alcoholism   248 of 323 pathways"
## [1] "Querying.............  Bacterial invasion of epithelial cells   249 of 323 pathways"
## [1] "Querying.............  Vibrio cholerae infection   250 of 323 pathways"
## [1] "Querying.............  Epithelial cell signaling in Helicobacter pylori infection   251 of 323 pathways"
## [1] "Querying.............  Pathogenic Escherichia coli infection   252 of 323 pathways"
## [1] "Querying.............  Shigellosis   253 of 323 pathways"
## [1] "Querying.............  Salmonella infection   254 of 323 pathways"
## [1] "Querying.............  Pertussis   255 of 323 pathways"
## [1] "Querying.............  Legionellosis   256 of 323 pathways"
## [1] "Querying.............  Yersinia infection   257 of 323 pathways"
## [1] "Querying.............  Leishmaniasis   258 of 323 pathways"
## [1] "Querying.............  Chagas disease   259 of 323 pathways"
## [1] "Querying.............  African trypanosomiasis   260 of 323 pathways"
## [1] "Querying.............  Malaria   261 of 323 pathways"
## [1] "Querying.............  Toxoplasmosis   262 of 323 pathways"
## [1] "Querying.............  Amoebiasis   263 of 323 pathways"
## [1] "Querying.............  Staphylococcus aureus infection   264 of 323 pathways"
## [1] "Querying.............  Tuberculosis   265 of 323 pathways"
## [1] "Querying.............  Hepatitis C   266 of 323 pathways"
## [1] "Querying.............  Hepatitis B   267 of 323 pathways"
## [1] "Querying.............  Measles   268 of 323 pathways"
## [1] "Querying.............  Human cytomegalovirus infection   269 of 323 pathways"
## [1] "Querying.............  Influenza A   270 of 323 pathways"
## [1] "Querying.............  Human papillomavirus infection   271 of 323 pathways"
## [1] "Querying.............  Human T-cell leukemia virus 1 infection   272 of 323 pathways"
## [1] "Querying.............  Kaposi sarcoma-associated herpesvirus infection   273 of 323 pathways"
## [1] "Querying.............  Herpes simplex virus 1 infection   274 of 323 pathways"
## [1] "Querying.............  Epstein-Barr virus infection   275 of 323 pathways"
## [1] "Querying.............  Human immunodeficiency virus 1 infection   276 of 323 pathways"
## [1] "Querying.............  Coronavirus disease - COVID-19   277 of 323 pathways"
## [1] "Querying.............  Pathways in cancer   278 of 323 pathways"
## [1] "Querying.............  Transcriptional misregulation in cancer   279 of 323 pathways"
## [1] "Querying.............  Viral carcinogenesis   280 of 323 pathways"
## [1] "Querying.............  Chemical carcinogenesis - DNA adducts   281 of 323 pathways"
## [1] "Querying.............  Proteoglycans in cancer   282 of 323 pathways"
## [1] "Querying.............  MicroRNAs in cancer   283 of 323 pathways"
## [1] "Querying.............  Chemical carcinogenesis - receptor activation   284 of 323 pathways"
## [1] "Querying.............  Chemical carcinogenesis - reactive oxygen species   285 of 323 pathways"
## [1] "Querying.............  Colorectal cancer   286 of 323 pathways"
## [1] "Querying.............  Renal cell carcinoma   287 of 323 pathways"
## [1] "Querying.............  Pancreatic cancer   288 of 323 pathways"
## [1] "Querying.............  Endometrial cancer   289 of 323 pathways"
## [1] "Querying.............  Glioma   290 of 323 pathways"
## [1] "Querying.............  Prostate cancer   291 of 323 pathways"
## [1] "Querying.............  Thyroid cancer   292 of 323 pathways"
## [1] "Querying.............  Basal cell carcinoma   293 of 323 pathways"
## [1] "Querying.............  Melanoma   294 of 323 pathways"
## [1] "Querying.............  Bladder cancer   295 of 323 pathways"
## [1] "Querying.............  Chronic myeloid leukemia   296 of 323 pathways"
## [1] "Querying.............  Acute myeloid leukemia   297 of 323 pathways"
## [1] "Querying.............  Small cell lung cancer   298 of 323 pathways"
## [1] "Querying.............  Non-small cell lung cancer   299 of 323 pathways"
## [1] "Querying.............  Breast cancer   300 of 323 pathways"
## [1] "Querying.............  Hepatocellular carcinoma   301 of 323 pathways"
## [1] "Querying.............  Gastric cancer   302 of 323 pathways"
## [1] "Querying.............  Central carbon metabolism in cancer   303 of 323 pathways"
## [1] "Querying.............  Choline metabolism in cancer   304 of 323 pathways"
## [1] "Querying.............  PD-L1 expression and PD-1 checkpoint pathway in cancer   305 of 323 pathways"
## [1] "Querying.............  Asthma   306 of 323 pathways"
## [1] "Querying.............  Autoimmune thyroid disease   307 of 323 pathways"
## [1] "Querying.............  Inflammatory bowel disease   308 of 323 pathways"
## [1] "Querying.............  Systemic lupus erythematosus   309 of 323 pathways"
## [1] "Querying.............  Rheumatoid arthritis   310 of 323 pathways"
## [1] "Querying.............  Allograft rejection   311 of 323 pathways"
## [1] "Querying.............  Graft-versus-host disease   312 of 323 pathways"
## [1] "Querying.............  Hypertrophic cardiomyopathy   313 of 323 pathways"
## [1] "Querying.............  Arrhythmogenic right ventricular cardiomyopathy   314 of 323 pathways"
## [1] "Querying.............  Dilated cardiomyopathy   315 of 323 pathways"
## [1] "Querying.............  Diabetic cardiomyopathy   316 of 323 pathways"
## [1] "Querying.............  Viral myocarditis   317 of 323 pathways"
## [1] "Querying.............  Lipid and atherosclerosis   318 of 323 pathways"
## [1] "Querying.............  Fluid shear stress and atherosclerosis   319 of 323 pathways"
## [1] "Querying.............  Valine, leucine and isoleucine biosynthesis   320 of 323 pathways"
## [1] "Querying.............  Neomycin, kanamycin and gentamicin biosynthesis   321 of 323 pathways"
## [1] "Querying.............  Protein digestion and absorption   322 of 323 pathways"
## [1] "Querying.............  Nicotine addiction   323 of 323 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

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 4.1.1 (2021-08-10)
## Platform: x86_64-pc-linux-gnu (64-bit)
## Running under: Ubuntu 20.04.3 LTS
## 
## Matrix products: default
## BLAS:   /home/biocbuild/bbs-3.14-bioc/R/lib/libRblas.so
## LAPACK: /home/biocbuild/bbs-3.14-bioc/R/lib/libRlapack.so
## 
## locale:
##  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
##  [3] LC_TIME=en_GB              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      stats4    stats     graphics  grDevices utils     datasets 
## [8] methods   base     
## 
## other attached packages:
##  [1] png_0.1-7            qgraph_1.9           org.Hs.eg.db_3.14.0 
##  [4] graphite_1.40.0      StarBioTrek_1.20.0   miRNAtap_1.28.0     
##  [7] AnnotationDbi_1.56.0 IRanges_2.28.0       S4Vectors_0.32.0    
## [10] Biobase_2.54.0       BiocGenerics_0.40.0  BiocStyle_2.22.0    
## 
## loaded via a namespace (and not attached):
##   [1] backports_1.2.1        Hmisc_4.6-0            plyr_1.8.6            
##   [4] igraph_1.2.7           splines_4.1.1          usethis_2.1.2         
##   [7] GenomeInfoDb_1.30.0    ggplot2_3.3.5          digest_0.6.28         
##  [10] htmltools_0.5.2        magick_2.7.3           gdata_2.18.0          
##  [13] fansi_0.5.0            magrittr_2.0.1         checkmate_2.0.0       
##  [16] memoise_2.0.0          MLmetrics_1.1.1        cluster_2.1.2         
##  [19] ROCR_1.0-11            remotes_2.4.1          Biostrings_2.62.0     
##  [22] prettyunits_1.1.1      jpeg_0.1-9             colorspace_2.0-2      
##  [25] blob_1.2.2             rappdirs_0.3.3         xfun_0.27             
##  [28] dplyr_1.0.7            callr_3.7.0            crayon_1.4.1          
##  [31] RCurl_1.98-1.5         jsonlite_1.7.2         graph_1.72.0          
##  [34] survival_3.2-13        miRNAtap.db_0.99.10    glue_1.4.2            
##  [37] gtable_0.3.0           zlibbioc_1.40.0        XVector_0.34.0        
##  [40] pkgbuild_1.2.0         abind_1.4-5            scales_1.1.1          
##  [43] DBI_1.1.1              Rcpp_1.0.7             htmlTable_2.3.0       
##  [46] tmvnsim_1.0-2          foreign_0.8-81         bit_4.0.4             
##  [49] proxy_0.4-26           Formula_1.2-4          sqldf_0.4-11          
##  [52] htmlwidgets_1.5.4      httr_1.4.2             RColorBrewer_1.1-2    
##  [55] lavaan_0.6-9           ellipsis_0.3.2         pkgconfig_2.0.3       
##  [58] nnet_7.3-16            sass_0.4.0             utf8_1.2.2            
##  [61] tidyselect_1.1.1       rlang_0.4.12           reshape2_1.4.4        
##  [64] munsell_0.5.0          tools_4.1.1            cachem_1.0.6          
##  [67] cli_3.0.1              gsubfn_0.7             generics_0.1.1        
##  [70] RSQLite_2.2.8          devtools_2.4.2         fdrtool_1.2.16        
##  [73] evaluate_0.14          stringr_1.4.0          fastmap_1.1.0         
##  [76] yaml_2.2.1             processx_3.5.2         knitr_1.36            
##  [79] bit64_4.0.5            fs_1.5.0               purrr_0.3.4           
##  [82] KEGGREST_1.34.0        glasso_1.11            pbapply_1.5-0         
##  [85] nlme_3.1-153           compiler_4.1.1         rstudioapi_0.13       
##  [88] curl_4.3.2             e1071_1.7-9            testthat_3.1.0        
##  [91] tibble_3.1.5           bslib_0.3.1            pbivnorm_0.6.0        
##  [94] stringi_1.7.5          highr_0.9              ps_1.6.0              
##  [97] desc_1.4.0             lattice_0.20-45        Matrix_1.3-4          
## [100] psych_2.1.9            vctrs_0.3.8            pillar_1.6.4          
## [103] lifecycle_1.0.1        BiocManager_1.30.16    jquerylib_0.1.4       
## [106] data.table_1.14.2      bitops_1.0-7           corpcor_1.6.10        
## [109] R6_2.5.1               latticeExtra_0.6-29    bookdown_0.24         
## [112] gridExtra_2.3          sessioninfo_1.1.1      gtools_3.9.2          
## [115] assertthat_0.2.1       pkgload_1.2.3          chron_2.3-56          
## [118] proto_1.0.0            rprojroot_2.0.2        withr_2.4.2           
## [121] SpidermiR_1.24.0       mnormt_2.0.2           GenomeInfoDbData_1.2.7
## [124] parallel_4.1.1         rpart_4.1-15           class_7.3-19          
## [127] rmarkdown_2.11         base64enc_0.1-3

References

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

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.

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

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.”