Nanoinformatics: developing new computing applications for nanomedicine

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 open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment 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 information 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

Using natural language processing techniques to inform research on nanotechnology

Literature in the field of nanotechnology is exponentially increasing with more and more engineered nanomaterials being created, characterized, and tested for performance and safety. With the deluge of published data, there is a need for natural language processing approaches to semi-automate the cataloguing of engineered nanomaterials and their associated physico-chemical properties, performance, exposure scenarios, and biological effects. In this paper, we review the different informatics methods that have been applied to patent mining, nanomaterial/device characterization, nanomedicine, and environmental risk assessment. Nine natural language processing (NLP)-based tools were identified: NanoPort, NanoMapper, TechPerceptor, a Text Mining Framework, a Nanodevice Analyzer, a Clinical Trial Document Classifier, Nanotoxicity Searcher, NanoSifter, and NEIMiner. We conclude with recommendations for sharing NLP-related tools through online repositories to broaden participation in nanoinformatics

(Q)SAR Modelling of Nanomaterial Toxicity - A Critical Review

There is an increasing recognition that nanomaterials pose a risk to human health, and that the novel engineered nanomaterials (ENMs) in the nanotechnology industry and their increasing industrial usage poses the most immediate problem for hazard assessment, as many of them remain untested. The large number of materials and their variants (different sizes and coatings for instance) that require testing and ethical pressure towards non-animal testing means that expensive animal bioassay is precluded, and the use of (quantitative) structure activity relationships ((Q)SAR) models as an alternative source of hazard information should be explored. (Q)SAR modelling can be applied to fill the critical knowledge gaps by making the best use of existing data, prioritize physicochemical parameters driving toxicity, and provide practical solutions to the risk assessment problems caused by the diversity of ENMs. This paper covers the core components required for successful application of (Q)SAR technologies to ENMs toxicity prediction, and summarizes the published nano-(Q)SAR studies and outlines the challenges ahead for nano-(Q)SAR modelling. It provides a critical review of (1) the present status of the availability of ENMs characterization/toxicity data, (2) the characterization of nanostructures that meets the need of (Q)SAR analysis, (3) the summary of published nano-(Q)SAR studies and their limitations, (4) the in silico tools for (Q)SAR screening of nanotoxicity and (5) the prospective directions for the development of nano-(Q)SAR models

Nanoinformatics knowledge infrastructures: bringing efficient information management to nanomedical research

Nanotechnology represents an area of particular promise and significant opportunity across multiple scientific disciplines. Ongoing nanotechnology research ranges from the characterization of nanoparticles and nanomaterials to the analysis and processing of experimental data seeking correlations between nanoparticles and their functionalities and side effects. Due to their special properties, nanoparticles are suitable for cellular-level diagnostics and therapy, offering numerous applications in medicine, e.g. development of biomedical devices, tissue repair, drug delivery systems and biosensors. In nanomedicine, recent studies are producing large amounts of structural and property data, highlighting the role for computational approaches in information management. While in vitro and in vivo assays are expensive, the cost of computing is falling. Furthermore, improvements in the accuracy of computational methods (e.g. data mining, knowledge discovery, modeling and simulation) have enabled effective tools to automate the extraction, management and storage of these vast data volumes. Since this information is widely distributed, one major issue is how to locate and access data where it resides (which also poses data-sharing limitations). The novel discipline of nanoinformatics addresses the information challenges related to nanotechnology research. In this paper, we summarize the needs and challenges in the field and present an overview of extant initiatives and efforts

Nanoinformatics: a new area of research in nanomedicine

Over a decade ago, nanotechnologists began research on applications of nanomaterials for medicine. This research has revealed a wide range of different challenges, as well as many opportunities. Some of these challenges are strongly related to informatics issues, dealing, for instance, with the management and integration of heterogeneous information, defining nomenclatures, taxonomies and classifications for various types of nanomaterials, and research on new modeling and simulation techniques for nanoparticles. Nanoinformatics has recently emerged in the USA and Europe to address these issues. In this paper, we present a review of nanoinformatics, describing its origins, the problems it addresses, areas of interest, and examples of current research initiatives and informatics resources. We suggest that nanoinformatics could accelerate research and development in nanomedicine, as has occurred in the past in other fields. For instance, biomedical informatics served as a fundamental catalyst for the Human Genome Project, and other genomic and ?omics projects, as well as the translational efforts that link resulting molecular-level research to clinical problems and findings

Reproductive Toxicity and Life History Study of Silver Nanoparticle Effect, Uptake and Transport in Arabidopsis thaliana

Concerns about nanotechnology have prompted studies on how the release of these engineered nanoparticles impact our environment. Herein, the impact of 20 nm silver nanoparticles (AgNPs) on the life history traits of Arabidopsis thaliana was studied in both above- and below-ground parts, at macroscopic and microscopic scales. Both gross phenotypes (in contrast to microscopic phenotypes) and routes of transport and accumulation were investigated from roots to shoots. Wild type Arabidopsis growing in soil, regularly irrigated with 75 μg/L of AgNPs, did not show any obvious morphological change. However, their vegetative development was prolonged by two to three days and their reproductive growth shortened by three to four days. In addition, the germination rates of offspring decreased drastically over three generations. These findings confirmed that AgNPs induce abiotic stress and cause reproductive toxicity in Arabidopsis. To trace transport of AgNPs, this study also included an Arabidopsis reporter line genetically transformed with a green fluorescent protein and grown in an optical transparent medium with 75 μg/L AgNPs. AgNPs followed three routes: (1) At seven days after planting (DAP) at S1.0 (stages defined by Boyes et al. 2001 [41]), AgNPs attached to the surface of primary roots and then entered their root tips; (2) At 14 DAP at S1.04, as primary roots grew longer, AgNPs gradually moved into roots and entered new lateral root primordia and root hairs; (3) At 17 DAP at S1.06 when the Arabidopsis root system had developed multiple lateral roots, AgNPs were present in vascular tissue and throughout the whole plant from root to shoot. In some cases, if cotyledons of the Arabidopsis seedlings were immersed in melted transparent medium, then AgNPs were taken up by and accumulated in stomatal guard cells. These findings in Arabidopsis are the first to document specific routes and rates of AgNP uptake in vivo and in situ

Nanoinformatics: a new area of research in nanomedicine

pre-printAbstract: Over a decade ago, nanotechnologists began research on applications of nanomaterials for medicine. This research has revealed a wide range of different challenges, as well as many opportunities. Some of these challenges are strongly related to informatics issues, dealing, for instance, with the management and integration of heterogeneous information, defining nomenclatures, taxonomies and classifications for various types of nanomaterials, and research on new modeling and simulation techniques for nanoparticles. Nanoinformatics has recently emerged in the USA and Europe to address these issues. In this paper, we present a review of nanoinformatics, describing its origins, the problems it addresses, areas of interest, and examples of current research initiatives and informatics resources. We suggest that nanoinformatics could accelerate research and development in nanomedicine, as has occurred in the past in other fields. For instance, biomedical informatics served as a fundamental catalyst for the Human Genome Project, and other genomic and -omics projects, as well as the translational efforts that link resulting molecular-level research to clinical problems and findings

Investigating Mechanisms of Nanotoxicity of a Next-Generation Lithium Cobalt Oxide Nanomaterial

Commercial use of engineered nanomaterials (ENMs; materials in the range of 1-100 nm) has grown dramatically since the discovery of the means to observe, characterize, and controllably synthesize these materials at the end of the 20th century. Today, ENMs represent a global market valued in the trillions of dollars, incorporated into products because of the unique properties they confer, including increased strength, catalytic activity, and interactions with light. In this time, ENMs have also grown from relatively simple first-generation materials, such as Au, Ag, and carbon ENMs, to complex next-generation materials incorporating numerous elements into materials with complex secondary structures, such as the lithium intercalating complex metal oxide cathode materials used in lithium-ion batteries (LIBs). The commercial use of ENMs results in ENM waste on the order of hundreds of thousands to millions of tons annually, enough that ENM waste represents an emerging environmental concern. LIB cathode waste alone amounts to hundreds of thousands of tons annually, with little of this recycled. As the development and use of ENMs has grown, alongside it has grown the field of nanotoxicology, determined to understand if the same properties, such as size, core material, surface area, and surface chemistry, that confer useful properties to ENMs also imbue them with toxicity toward biological systems. However, while the diversity of ENMs has grown, the field of nanotoxicology has focused to a large extent on examining the toxicity of first-generation materials (e.g., Au and Ag) and on oxidative stress as the mechanism of nanotoxicity. Oxidative stress as a mechanism of nanotoxicity is understood as a general mechanism of cellular damage by reactive oxygen species (ROS). However, simple observation of ROS is not explanatory of ENM toxicity, as ROS are not only damaging molecules, but are involved in regulation of critical cellular processes including metabolism, growth, and differentiation. Therefore, the presence of redox-sensitive components in these pathways makes them susceptible to specific interactions with redox-active ENMs or ROS even at sublethal, physiologically relevant concentrations. Environmental nanotoxicology has also focused to a large degree on the aquatic invertebrate Daphnia magna, whose wide use in the field of toxicology more generally makes it a broadly applicable model. However, D. magna reside in the water column, while many ENMs are expected to settle in the aquatic environment and concentrate in the sediment, making testing on sediment-dwelling organisms such as the invertebrate midge species Chironomus riparius important for understanding the potential environmental impacts of ENMs. Overcoming these limitations of nanotoxicology requires testing of next-generation ENMs, including on sediment-dwelling organisms, and the exploration of mechanisms of nanotoxicology at the molecular level, beyond simple oxidative stress. A useful framework to guide the elucidation of this molecular-level understanding is the adverse outcome pathway (AOP). In this framework, the interaction of a toxicant such as an ENM with a biological system is understood from the standpoint of a molecular interaction between the toxicant and a biological component (called the molecular initiating event; MIE), which results in a series of key events (KEs) that occur in the biological system in response to this impact, and ultimately causes an adverse outcome (AO) for the biological system, such as the death of an organism or cell. By using molecular tools to interrogate ENM impacts at each stage of this process, it is possible to trace observed AOs through their series of associated KEs and ultimately down to the specific MIE(s). This thesis sought to address the shortcomings of current nanotoxicology by using molecular methods to inform an AOP for the toxicity of the next-generation complex metal oxide LIB cathode material lithium cobalt oxide (LCO) in sediment-dwelling Chironomus riparius and in Daphnia magna. Results of these investigations demonstrate oxidation of the Fe-S center of energy metabolism enzyme aconitase as an MIE of LCO toxicity, disrupted heme synthesis and energy metabolism as KEs by targeted and global gene expression analysis, KEs of altered metabolic gene expression and metabolite levels toward energy production by combined global gene expression and non-targeted metabolomics, and AOs of reduced growth and delayed development. This work thus demonstrates the paradigm by which ENM toxicity can be understood at the molecular level, including the interconnections of the MIE, KEs, and AOs for LCO within the AOP framework. Furthermore, this AOP, placed in the context of the literature, suggest a general AOP for toxicity of metal oxide ENMs in which the redox chemistry of a metal oxide ENM causes oxidation of redox-sensitive biological components, such as proteins and cofactors involved in energy metabolism, disrupting critical processes including energy metabolism, and ultimately disrupting growth and development at the organism level. Further exploration of the details of this AOP represent an exciting future direction for the investigation of the interaction of metal oxide ENMs with biological systems

Oxidative Stress-Induced Formation of Covalently Linked Ribulose-1,5-bisphosphate Carboxylase/Oxygenase Large Subunit Dimer in Tobacco Plants

Objective: Many abiotic stresses cause the excessive accumulation of reactive oxygen species known as oxidative stress. While analyzing the effects of oxidative stress on tobacco, we noticed the increased accumulation of a specific protein in extracts from plants treated with the oxidative-stress inducing herbicide paraquat which promotes the generation of reactive oxygen species primarily in chloroplasts. The primary objectives of this study were to identify this protein and to determine if its accumulation is indeed a result of oxidative stress. Results: Here we show that the paraquat-induced protein is a covalently linked dimer of the large subunit of ribulose-1,5-bisphosphate carboxylase (LSU). Increased accumulation of this LSU dimer was also observed in tobacco plants exposed to ultra-small anatase titanium dioxide nanoparticles (nTiO2), which because of their surface reactivity cause oxidative stress by promoting the generation of superoxide anion. nTiO2 nanoparticle treatments also caused a decline in the chloroplast thylakoid proteins cytochrome f and chlorophyll a/b binding protein, thus confirming that covalent LSU dimer formation coincides with loss of chloroplast function