Nanoinformatics: developing new computing applications for nanomedicine Victor Maojo • Martin Fritts • Fernando Martin-Sanchez • Diana De la Iglesia • Raul E. Cachau • Miguel Garcia-Remesal • Jose Crespo • Joyce A. Mitchell • Alberto Anguita • Nathan Baker • Jose Maria Barreiro • Sonia E. Benitez • Guillermo De la Calle • Julio C. Facelli • Peter Ghazal • Antoine Geissbuhler • Fernando Gonzalez-Nilo • Norbert Graf • Pierre Grangeat • Isabel Hermosilla • Rada Hussein • Josipa Kern • Sabine Koch • Yannick Legre • Victoria Lopez-Alonso • Guillermo Lopez-Campos • Luciano Milanesi • Vassilis Moustakis • Cristian Munteanu • Paula Otero • Alejandro Pazos • David Perez-Rey • George Potamias • Ferran Sanz • Casimir Kulikowski Abstract Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials V. Maojo (E3) • D. De la Iglesia • M. Garcia-Remesal • J. Crespo • A. Anguita • J. M. Barreiro • G. De la Calle • D. Perez-Rey Biomedical Informatics Group, Departamento de Inteligencia Artificial, Faculdad de Informatica, Universidad Politecnica de Madrid, Boadilla del Monte, 28660 Madrid, Spain e-mail: [email protected] M. Fritts SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, MD, USA F. Martin-Sanchez Health and Biomedical Informatics Research Laboratory Medical School-IBES, The University of Melbourne, Parkville, VIC, Australia R. E. Cachau Advanced Biomedical Computing Center, National Cancer Institute, SAIC-Frederick Inc., Frederick, MD, USA J. A. Mitchell • J. C. Facelli Biomedical Informatics Department, University of Utah, Salt Lake City, Utah, USA N. Baker Pacific Northwest National Laboratory, Richland, WA, USA S. E. Benitez • P. Otero Department of Medical Informatics, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treat- P. Ghazal Division of Pathway Medicine and Centre for Systems Biology Edinburgh, University of Edinburgh, Edinburgh, UK A. Geissbuhler Division of Medical Informatics, University Hospitals of Geneva, Geneva, Switzerland F. Gonzalez-Nilo Center for Bioinformatics and Molecular Simulation, Universidad de Talca, Talca, Chile N. Graf Department of Pediatric Oncology and Hematology, University of the Saarland, Homburg, Germany P. Grangeat Laboratoire d'Electronique et de Technologie de l'lnformation (LETI), MINATEC Campus, Commissariat a l'Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France I. Hermosilla • V. Lopez-Alonso • G. Lopez-Campos Department of Medical Bioinformatics, Institute of Health "Carlos III", Madrid, Spain R. Hussein Information Technology Institute, Ministry of Communications and Information Technology, Cairo, Egypt J. Kern Department of Medical Statistics, Epidemiology and Medical Informatics, Andrija Stampar School of Public Health, Zagreb University Medical School, Zagreb, Croatia S. Koch Health Informatics Centre, Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden Y. Legre Health Grid Organization, Clermont-Ferrand, France L. Milanesi Institute of Biomedical Technology, National Research Council, Milan, Italy V. Moustakis Technical University of Crete, Chania, Crete, Greece V. Moustakis • G. Potamias Institute of Computer Science, FORTH, Heraklion, Crete, Greece C. Munteanu • A. Pazos Department of Information and Communication Technologies, University of A Coruna, A Coruna, Spain F. Sanz Biomedical Informatics Research Programme (GRIB), IMIM, Universitat Pompeu Fabra, Barcelona, Spain C. Kulikowski Department of Computer Science, Rutgers, The State University of New Jersey, Newark, USA ment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce infor­ mation related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others. Keywords Nanoinformatics • Computing • Nanotechnology • Bioinformatics • Medical Informatics • Nanomedicine 1 Introduction Over the past five decades many computing methods and applications have arisen in the context of biomedicine, leading to interdisciplinary areas such as medical infor­ matics, bioinformatics and others [1-3]. These biomedical-related informatics disci­ plines span a wide range of scientific and technological approaches to solve complex problems, including, among others, data and knowledge integration methods, biomed­ ical ontologies and vocabularies, data and text mining, systems interoperability, DNA and RNA sequencing, medical decision support, predicting the relationships between gene mutations and diseases, the development of standards for data representation and exchange, or the development of informatics methods and tools for integrating multi­ level data and creating multi-scale simulations of biomedical systems. Informaticians have successfully contributed to these areas, leading to outstanding results such as the Human Genome and other -omics projects, the computerization of clinical practice or the creation of computerized systems for decision support [4]. The authors have been active in informatics research supporting a number of projects in the past decades and pioneered significant examples such as, among others, medical expert systems [5-7]. After various decades of research on such biomedical systems, a challenging new field, nanomedicine, which promises to deliver scientific and technological break­ throughs that could transform medicine, is beginning to receive attention from the scientific community, including informaticians [8]. To our knowledge, no paper has been published, at the time of writing, in the computing literature about nanoinformatics. Figure 1 presents an analysis of these references, using the goPubmed [9] facility. In this context, one particular challenging issue, which remains mostly unexplored, is the application of computing to nanomedicine. To advance research in this field, requirements for data, information and knowledge management need to be specified, and are substantial. While research in this area is commonly associated with nanotech­ nology there are many topics where computational methods are themselves critical to advance research and support professional practice. For instance, we have identified TbAiearS Pu the aliens > loo Terms Pub Ik a/n'0n4 O 2009 11 a Nanotnthnotogry 51 O :oio 10 2 S 0 Humans 31 O 2011 9 o ^ d Technology 23 Q 2006 9 z < £ Medicine U O 2006 a Hi Delivery Of HeanhCSre 10 O 2005 7 it Nanosmxiure? 14 O 2004 5 11 ii Nanomeditine 13 O 200 T 4 '£ M Equipmentanfl Supplies, 17 Q 2001 1 H Health Can* 11 M Electrons 10 It* Wars Publications TopTfrrmS PublieabOnf O 20QQ ?1H949 a Humans 70,319 O 2008 21 .452 g H Patflifls 30,41$ Q 2010 20,578 M, Eiiluabon Studies as Topic 21,953 O 2007 19,491 ** H. Algontnrns 71,494 Q 20ii 12.257 o^ .^du: 17,270 Q 2006 3794 h Middle Aged 10.43$ Q 2005 279 ^ H ReciroducibilnyiSTResuns 1 5,704 Q 2004 1 JD ~ B Dm* imerpretjijon, Siaii^dtai 14.922 O 2001 34 g** H Sensrlwriy and EpenfiLily 14,556 Q 2003 21 111 44 Irnti* InhJjn elaMn, Compuler-AsslSted 13.222 u ?oo: •a 5 O 20QO ia 'en "tears Publications r;; rgimi. Publications Q 3010 12,79$ N,!! ill-. 40,092 Q 2009 11,791 w H Proteins 39h301 Q 2003 10,42$ « Computational Biolocnf 35.787 Q 2011 10,059 1 H Genomics 32,41-5 © 2007 0,511 5 •:••:!.'• i 31,786 Q 2006 8.517 lomrn 29h015 O 2005 BJM2 g H Animus 26,745 Q 2004 6.277 M Prateamics 22h400 Q 2009 4,591 M proleoiw* 19,759 O 200? 3,264 I H AJgonlhms 15h719 Q 2001 ?H22& U 20O0 1,503 ibp 'tears Pupucatwns TOOTeiTrlS Publications O 20O9 107 Mi hi.m.irlT. 598 Q 2010 97 M .AJgomhms 343 U 20OB 90 n Evsiushfln studies as TbcHc 194 O 2011 84 JHi Pabenls 178 Q 2007 81 H Hithsmabcai computing 170 IE 11 O 200$ M Technology 170 Q 2004 n ill Animals 152 O 2005 $0 ita iy H BiomecFical Res earch 133 G 2003 57 I* Computational ffioloor 110 Q 2007 49 M knowledge 115 O 2000 37 Fig. 1 A comparative analysis among the references available in Medline with the terms "Nanotechnol- ogy Informatics", "Medical Informatics", "Bioinformatics" and "Biomedical Computing" carried out with goPubmed [9]. On the left side, is shown the number of publications per year (2000-present); on the right side, the top terms or most common keywords used in these publications various areas where significant research in informatics applied to nanomedicine is already underway [10,11]. These can be summarized in the following non-exhaustive list: - Nanoparticle characterization - Modeling and simulation - Imaging - Terminologies, ontologies and standards - Data Integration and Exchange - Systems' interoperability - Data and text mining for nanomedical research - Linking nano-information to computerized