Abstract
Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless ‘geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses. ACSN may also support patient stratification, prediction of treatment response and resistance to cancer drugs, as well as design of novel treatment strategies.
Highlights
Understanding of tumorigenesis has drastically improved recently owing to extensive studies of the implicated molecular mechanisms.[1]
The key canonical pathways, as they are RESULTS Atlas of Cancer Signalling Network (ACSN) concept and features depicted in the major pathway databases, represent the basis for depicting modules in ACSN, reflecting the consensus view of the scientific community on the pathways
ACSN graphically depicts molecular mechan- the requirement that the interactions and processes included to isms that occur in normal, healthy mammalian cells but that are this level of ACSN are supported by several frequently modified in cancer, underlying the hallmarks of cancer.[1]
Summary
Understanding of tumorigenesis has drastically improved recently owing to extensive studies of the implicated molecular mechanisms.[1] This knowledge mostly exists in a human-readable form, fragmented in scientific publications. This circumstance hampers the delineation of a global picture of cancer biology and prevents from efficient integration of high-throughput data and application of bioinformatics and systems biology approaches.[2]. Cancer research can benefit from the reconstruction of cellular signalling in the form of a comprehensive map, representing the complexity of pathway crosstalk[4] manifested by co-participation, interaction or co-regulation of molecular entities in several cell signalling processes. Understanding connections between molecular mechanisms is important for determining potential therapeutic intervention points.[5,6]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call