DrugTargetInspector: An assistance tool for patient treatment stratification.
Cancer is a large class of diseases that are characterized by a common set of features, known as the Hallmarks of cancer. One of these hallmarks is the acquisition of genome instability and mutations. This, combined with high proliferation rates and failure of repair mechanisms, leads to clonal evolution as well as a high genotypic and phenotypic diversity within the tumor. As a consequence, treatment and therapy of malignant tumors is still a grand challenge. Moreover, under selective pressure, e.g., caused by chemotherapy, resistant subpopulations can emerge that then may lead to relapse. In order to minimize the risk of developing multidrug-resistant tumor cell populations, optimal (combination) therapies have to be determined on the basis of an in-depth characterization of the tumor's genetic and phenotypic makeup, a process that is an important aspect of stratified medicine and precision medicine. We present DrugTargetInspector (DTI), an interactive assistance tool for treatment stratification. DTI analyzes genomic, transcriptomic, and proteomic datasets and provides information on deregulated drug targets, enriched biological pathways, and deregulated subnetworks, as well as mutations and their potential effects on putative drug targets and genes of interest. To demonstrate DTI's broad scope of applicability, we present case studies on several cancer types and different types of input -omics data. DTI's integrative approach allows users to characterize the tumor under investigation based on various -omics datasets and to elucidate putative treatment options based on clinical decision guidelines, but also proposing additional points of intervention that might be neglected otherwise. DTI can be freely accessed at http://dti.bioinf.uni-sb.de.
Center for Bioinformatics, Saarland University, Saarbrücken, Germany.|Saarbrücken Graduate School of Computer Science, Saarland University, Saarbrücken, Germany.
Lara
L
Schneider
Center for Bioinformatics, Saarland University, Saarbrücken, Germany.|Saarbrücken Graduate School of Computer Science, Saarland University, Saarbrücken, Germany.
Daniel
D
Stöckel
Center for Bioinformatics, Saarland University, Saarbrücken, Germany.|Saarbrücken Graduate School of Computer Science, Saarland University, Saarbrücken, Germany.
Tim
T
Kehl
Center for Bioinformatics, Eberhard-Karls-University, Tübingen, Germany.
Andreas
A
Gerasch
Department of Human Genetics, Medical School, Saarland University, Homburg, Germany.
Nicole
N
Ludwig
Department of Human Genetics, Medical School, Saarland University, Homburg, Germany.
Petra
P
Leidinger
Department of Cardiothoracic Surgery, Völklingen Heart Center, Völklingen, Germany.
Hanno
H
Huwer
Institute for Immunology, Johannes Gutenberg University Mainz, Mainz, Germany.
Stefan
S
Tenzer
Center for Bioinformatics, Eberhard-Karls-University, Tübingen, Germany.|Biomolecular Interactions, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Oliver
O
Kohlbacher
Institute of Computer Science, Johannes Gutenberg University Mainz, Mainz, Germany.
Andreas
A
Hildebrandt
Center for Bioinformatics, Eberhard-Karls-University, Tübingen, Germany.
Michael
M
Kaufmann
Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, Würzburg University, Würzburg, Germany.
Manfred
M
Gessler
Center for Bioinformatics, Saarland University, Saarbrücken, Germany.
Andreas
A
Keller
Department of Human Genetics, Medical School, Saarland University, Homburg, Germany.
Eckart
E
Meese
Department of Pediatric Oncology and Hematology, Medical School, Saarland University, Homburg, Germany.
Norbert
N
Graf
Center for Bioinformatics, Saarland University, Saarbrücken, Germany.
Hans-Peter
HP
Lenhof
D003658:Decision Making, Computer-Assisted; D023281:Genomics / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D018579:Patient Selection
analysis; molecular drug targets; multi-omics integrated; precision medicine; treatment decision making; web server