Maojo et al the representation of studies employing one or a combi- nation of technologies, focusing on the description of its experimental metadata (ie, sample characteristics, technology and measurement types, sample–data relationships). ISA- Tab standards and their extension to the nano level in ISA-TAB-Nano will allow the same standard formats for high-throughput screening, nanomaterial characterization data (physico-chemical, in vitro, and in vivo) and, possibly, in silico data as well. Another significant example involves the development of standards for the minimum information required to character- ize nanomaterials115 – which extend previous efforts carried out for microarrays – and for harmonization of formats for data sharing. Impact The amount of information on nanoparticle toxicity is increasing, suggesting that a wide range of characteristics may mediate and determine the scale, dynamics, and health and environmental impact of adverse effects – and of current therapeutics. Initial results, from both animal studies and in vitro experiments, suggest that the type, size, and mode of utilization of nanoparticles may produce different effects on cell cultures.116 Understanding the toxicity mechanisms and effects of nanoscale materials – nanotoxicology – is the most critical problem now faced by nanomedical technology. The need for managing this information and linking it with specific patient data follows directly. There are various nanoscale materials for biological application that have failed because of their toxicity.45,109,110 This failure is due to the complexity of living organisms, which makes it difficult to predict the consequences (ie, adverse reactions) of inserting a material into biological systems: the toxicity of some nanomaterials involves very complex pathways as well as specific interactions between biological tissues and synthetic materials and the transformations those materials may undergo. All these issues point to the need for diverse informatics methods and tools to augment basic research results and bring together information from all relevant lines of research and clinical tests. Annotating the literature pres- ents considerable challenges both in theory and in practice. For instance, to alert researchers as to whether a particular nanomaterial has been sufficiently characterized, whether the methods used to characterize the nanomaterial and its interactions were validated, whether the models used were appropriate, or whether invalid conclusions might have been drawn. As mentioned, we are carrying out research on some of these issues. 3876 submit your manuscript | www.dovepress.com Dovepress Dovepress We summarize different aspects of nanoinformatics and its relevance to international research in Figure 1. In this figure, the various areas on which nanoinformatics can have a tremendous impact in the future are shown. We have classified these potential impact areas into eight categories: (1) industrial, (2) economic, (3) international collaboration, (4) national policy, (5) informatics, (6) societal, (7) educational, and (8) scientific. For expanded information on these topics, The ACTION-Grid White Paper is publicly available.80 A pervasive nanoinformatics problem is poor quality of available data, especially in terms of its reliability and reproducibility. This is due to various reasons, including: • the lack of development and utilization of validated methods for characterization of the nanomaterials and their properties • the incomplete characterization of nanomaterials and the lack of reference material to be used in the assays; the lack of curation and annotation of available data so that a measure of its reliability can be provided • the need for training materials for standard assays; the rise of multiple silos for nanotech data • the problems in federating those silos into a searchable system • the integration with –omics and system biology data • and the need for a set of ontologies that allows mapping and navigation among different ontologies for different disciplines through a harmonized system of concept definitions. A key issue is that nanoinformatics should not be just a support technology but a fundamental approach to integrating the various areas of research and translation needed for the field within a reasonable time. The diverse nano products cannot succeed without better characteriza- tion, validated methods, better training, and informatics systems that permit practitioners to cope with the massively large amount of information needed to properly utilize the technology. This is an urgent need. How will a practic- ing physician cope with all the different tests, treatment options, massively complex diagnosis decision aids, and so on, without informatics systems? Nanotechnology offers the hope of developing and testing these systems now so that we develop flexible methods of expanding them as our knowledge grows. Finally, researchers, designers, clinicians, practitioners, information brokers, and regulators face a critical issue of coping with a myriad of large information sources, for which nanoinformatics methods and tools are absolutely necessary. On balance, the persistence of prob- lems within the entire scientific community should also International Journal of Nanomedicine 2012:7