Abstract graphic file with name ao4c06708_0008.jpg Humans encounter diverse environmental factors which can have impact on their health. One such environmental factor is ultraviolet (UV) radiation, which is part of the physical component of the exposome. UV radiation is the leading cause of skin cancer and is a significant global health concern. A large body of published research has been conducted to uncover the mechanisms underlying the adverse outcomes of UV radiation exposure on living beings. These studies involve identifying the biomolecules induced upon UV radiation exposure. A few previous efforts have attempted to compile this information in the form of a database, but such earlier efforts have certain limitations. To fill this gap, we present a structured database named UVREK (UltraViolet Radiation Expression Knowledgebase), containing manually curated data on biomolecules induced by UV radiation exposure from the published literature. UVREK has compiled information on 985 genes, 470 proteins, 54 metabolites, and 77 miRNAs along with their metadata. Thereafter, an enrichment analysis performed on the human gene set of the UVREK database showed the importance of transcription-related processes in UV-related response and enrichment of pathways involved in cancer and aging. While significantly contributing toward characterizing the physical component of the exposome, we expect that the compiled data in UVREK will serve as a valuable resource for the development of better UV protection mechanisms such as UV sensors and sunscreens. Noteworthily, UVREK is the only resource to date compiling varied types of biomolecular responses to UV radiation with the corresponding metadata. UVREK is openly accessible at [34]https://cb.imsc.res.in/uvrek/. Introduction Humans are constantly exposed to myriad stressors in the environment that have impact on biological processes and eventually health. Such environmental exposures are referred to as “exposome”, which encapsulates the entire spectrum of environmental influences encountered by individuals throughout their lifetime. Specifically, human exposome encompasses chemical, physical, biological and social factors, which play a significant role in shaping our health and well-being.^[35]1−[36]6 In terms of understanding the impact of exposome on health, significant research effort has been devoted toward characterizing the chemical component of the exposome. These research efforts on chemical exposome include the Blood Exposome,^[37]7,[38]8 CTD,^[39]9 DEDuCT,^[40]10,[41]11 ExHuMId,^[42]12 Exposome-Explorer,^[43]13,[44]14,[45]2 FCCP,^[46]15 Human Indoor Exposome Database,^[47]16 NeurotoxKb,^[48]17 TExAs,^[49]18 T3DB,^[50]19,[51]20 ViCEKb^[52]21 among others. In contrast to the chemical exposome, much less effort has been devoted toward characterizing the physical component of the exposome and its impact on human health. Physical components (or stressors) in the exposome include heat, noise and radiation, which can play a substantial role in shaping human health. Among these exposures, ultraviolet (UV) radiation constitutes a significant portion of everyday human exposure and exerts both harmful and beneficial effects.^[53]22−[54]25 UV radiation is a form of nonionizing radiation with a wavelength ranging from 100 to 400 nm, and accounts for 5% of the total solar spectrum.^[55]26,[56]27 Based on the wavelength, UV radiation is categorized into three groups namely, UVC (100–280 nm), UVB (280–315 nm) and UVA (315–400 nm). Note that the longer the wavelength, the deeper it can penetrate into the skin layers. In case of UV, UVA has the longest wavelength and is capable of reaching the dermis of the skin. UVB mostly affects the epidermis and is capable of reaching the papillary dermis of skin.^[57]24,[58]27 UVC radiation, which has the shortest wavelength among the UV types and is known for its germicidal effects,^[59]28 gets filtered by atmospheric ozone and does not reach the skin in natural conditions. UV radiation exposure is a major environmental factor with impact on skin health and contributes significantly to skin aging. It also induces DNA damage, oxidative stress, free radical production, cell proliferation and inflammation, photoreactions and immunosuppression, which are all linked to tumorigenesis.^[60]24,[61]29,[62]30 UV radiation also increases the risk of skin cancer and cataracts, and there is also evidence indicating that both UVB and UVA promote melanoma development.^[63]24,[64]31 Apart from the documented negative effects, UV radiation is also known to have positive effects. UV radiation is well-known to induce vitamin D production in the skin. It has also been reported to improve skin related conditions such as psoriasis, vitiligo and localized scleroderma.^[65]32 UV radiation induces nitric oxide production which in turn has effects such as blood pressure reduction,^[66]33 stimulation of pigmentation^[67]34 and antimicrobial activity.^[68]35 Due to these reasons, it is crucial to understand the biomolecular responses to UV radiation exposure, which in turn will enable the appropriate use of UV radiation for benefits or seek proper protection from unwarranted exposure.^[69]36,[70]26 As the information on biomolecules induced by UV radiation exposure from previous research is scattered across published literature, there is a need to compile such information in a structured database centered on UV radiation exposure and their subsequent biomolecular responses. In this direction, there have been few efforts toward the development of radiation-specific databases, such as UVGD 1.0,^[71]26 RadAtlas 1.0^[72]36 and the Radiation Genes database.^[73]37 However, RadAtlas 1.0 and the Radiation Genes database have compiled data related to ionizing radiation, while UVGD 1.0 does not compile information on the sampling time, dose, dosage rate, and other experimental details, and is also limited to gene-related data ([74]Table [75]1 ). Addressing these gaps, by including details such as sampling time, dose, dosage rate, and compilation of other experimental conditions under which a particular biomolecule was induced, is crucial for enhancing the utility of such a database from the perspective of future applications.^[76]38 Additionally, compiling data sets pertaining to diverse biomolecules such as gene, protein, metabolite, and miRNA expression profiles will provide a sophisticated platform for advancing our understanding of the biological impact of UV radiation exposure on human physiology. Table 1. Comparison of the Presence or Absence of Features in the UVREK Database with Two Previously Published Resources, Namely, UVGD 1.0^[77]26 and RadAtlas 1.0^[78]36. feature UVREK UVGD 1.0 RadAtlas 1.0 radiation type used yes no no dosage rate yes no no dose yes no no sampling time yes no no tested organisms human human human mouse rat tested cell/tissue type yes no no expression profile of genes yes yes yes number of compiled genes 985 663 598 expression profile of proteins yes no no expression profile of metabolites yes no no expression profile of miRNAs yes no no [79]Open in a new tab In this pursuit of establishing a UV-centric database, we systematically compiled and curated data on biomolecules induced by UV radiation exposure from 320 filtered published research articles, focusing specifically on studies involving humans and rodents. Specifically, we have compiled biomolecule response data obtained in normal, healthy cells or tissues exposed to UV radiation. This choice was influenced by the central motivation to contribute toward characterizing the physical component of the exposome, and including specimens of diseased state will distort this purpose.^[80]1,[81]6 Importantly, capturing responses in normal cells combined with dose information will help in the detection of potential biomarkers, which in turn can help in accessing the exposure level of an individual and help in risk stratification.^[82]39,[83]40,[84]4,[85]41 From the filtered articles, we meticulously collected biomolecular responses induced by UV radiation, including gene, protein, metabolite, and miRNA expression profiles, and mapped them to unique identifiers. This systematic approach resulted in a comprehensive compilation of biomolecule expression profiles, encompassing 985 genes, 470 proteins, 54 metabolites, and 77 miRNAs, sourced from studies spanning diverse cell types, tissue types, and experimental conditions. Subsequently, in order to widely share this curated data set, we created an online resource, UltraViolet Radiation Expression Knowledgebase (UVREK), which is openly accessible at: [86]https://cb.imsc.res.in/uvrek. Furthermore, to elucidate the molecular mechanisms and biological processes associated with UV radiation exposure, we performed extensive analyses such as GO term enrichment, pathway enrichment, and protein–protein interaction (PPI) network construction by leveraging the compiled data set in UVREK. These analyses yielded valuable insights into the biological effects of UV radiation and the intricate crosstalk between pathways involved in the response to UV exposure, thereby enhancing our understanding of UV-induced biomolecular changes. Results and Discussion UVREK: UltraViolet Radiation Expression Knowledgebase Humans are exposed to various forms of radiation, with UV radiation constituting a significant portion of everyday exposure. Our primary objective is to establish a comprehensive database focused on UV radiation exposure and the corresponding biomolecular response, encompassing gene, protein, metabolite, and miRNA expression profiles. By adhering to a structured workflow ([87]Methods), we filtered a curated set of 320 published research articles containing pertinent information on biomolecular responses triggered by UV radiation exposure across transcriptomic, proteomic, metabolomic, and miRNA expression studies. We collected the expression profiles of genes, proteins, metabolites, and miRNAs from the filtered research articles along with the corresponding metadata such as the experimental conditions, including details on tested organisms, organ or tissue or cell types, and dosage information (Methods). Finally, we annotated and compiled a nonredundant set of 985 genes, 470 proteins, 54 metabolites, and 77 miRNAs that have been shown to significantly respond to UV radiation exposure in published studies. Using this compiled data set, we built UVREK, a dedicated resource on UV radiation induced biomolecular expression profiles, which is openly accessible for academic research at: [88]https://cb.imsc.res.in/uvrek/. [89]Figure [90]1 visualizes the connections between data and metadata compiled in UVREK. That is, the figure shows the connections among various specifications of UV radiation exposures and biomolecular responses across the compiled data within UVREK. Moreover, [91]Figure [92]1 provides a comprehensive view of the nature of the filtered studies by displaying the interconnections between experimental conditions, specimen, and expression profiles. [93]Figure [94]2 displays screenshots of different pages and navigation options on the UVREK website, showcasing the structured online platform and user-friendly web interface of the database designed to ensure easy navigation and convenient access to the aggregated data for users ([95]Figure [96]2a). The “BROWSE” tab enables users to explore content in two ways: (i) Browse by UV type, or (ii) Browse by Biomolecules option ([97]Figure [98]2b). Browse by UV type enables users to explore data corresponding to various UV types: UVA, UVB, UVC, UVA+UVB and UVR-General (UV radiation-General). Similarly, Browse by Biomolecules enables users to explore UV radiation exposure induced biomolecule data on genes, proteins, metabolites, and miRNAs individually. [99]Figure [100]2c displays the tabular output from UVREK for genes induced by UV. [101]Figure [102]2c also displays a column in the tabular output which contains a link for the experimental information associated with the expression profile, facilitating access to all the metadata related to the corresponding data ([103]Figure [104]2d). In UVREK, clicking on the standardized identifiers (IDs) of the biomolecules will provide detailed information in a consolidated tabular format on all relevant literature and experimental conditions in which the biomolecules have been studied ([105]Figure [106]2e). Furthermore, the “SEARCH” tab allows users to query the UVREK database for biomolecules in two ways: (i) Search by ID, or (ii) Search by UV details. Search by ID enables users to search for the specific biomolecules using the corresponding identifiers or name and the organism name ([107]Figure [108]2f). Search by UV details allows users to search with details such as the organism name, UV radiation type, dose and dosage rate. The results of the “SEARCH” are presented in a tabulated format ([109]Figure [110]2g). Additionally, users can access data organized based on PMID through the “PMID” tab under the “SEARCH” tab. The “Experimental condition” tab within the “SEARCH” tab enables users to obtain a list of all biomolecules documented as differentially expressed under the specified experimental conditions. The “DOWNLOAD” tab provides users with access to flat files of the data available in the database. In addition, we have also created a GitHub repository where we have uploaded the flat files which can be accessed at [111]https://github.com/asamallab/UVREK. Figure 1. [112]Figure 1 [113]Open in a new tab Illustrative schematic depicting the connections between data and metadata. This figure showcases the interconnection between various specifications of UV radiation exposure and biomolecular responses. UV radiation is connected to experimental conditions and organisms in which experiments were conducted, as well as the study type, while biomolecules such as genes, proteins, metabolites, and miRNAs are linked to their mapping to unique identifiers in standard databases. Figure 2. [114]Figure 2 [115]Open in a new tab Screenshots illustrate the user interface and navigation features of the UVREK website. (a) Screenshot of the UVREK homepage which has a structured layout for ease of navigation and access to compiled data. (b) BROWSE tab showing two primary ways of exploring the content: Browse by UV type or Browse by Biomolecules. (c) BROWSE tab enables users to explore UV radiation exposure induced biomolecule data on genes, proteins, metabolites, and miRNAs, with results conveniently displayed in tabular formats. Last column of the tabular output has links to the associated experimental information, and clicking the corresponding link will lead to the page shown in part (d). (d) Screenshot of the page containing detailed information on the experimental conditions and other metadata associated with the expression profile of the corresponding biomolecule. (e) Screenshot of the tabular column obtained as a result of clicking on the standardized identifiers of a biomolecule. The resulting page displays information on all studies within UVREK in which the biomolecule has been reported. (f) Screenshot of the SEARCH page enabling users to query the compiled biomolecules in UVREK database based on their identifiers, UV-specific details, PMIDs or experimental conditions. (g) Screenshot of the results obtained in a tabular format from an example query search. Examples of Usage of the Database Here, we present two examples of potential use of the UVREK database. Use Case 1: Retrieve biomolecules differentially expressed under specific conditions Steps: * 1. Navigate to the “SEARCH” tab * 2. Select “Experimental condition” * 3. Enter the following details: + Organism Name: Homo sapiens + Tested Cell/Tissue: keratinocyte + UV Radiation Type: UVB-radiation + Dose (J/m^2): is less than 500 This will result in 494 entries that match the specified conditions. Use Case 2: Compare differential gene expression across species Scenario The user has a list of genes that are differentially expressed in Mus musculus after exposure to UVB-radiation at 50 J/m^2. The user subsequently wants to find genes that are differentially expressed in Homo sapiens under similar conditions. Steps: * 1. Navigate to the “SEARCH” tab. * 2. Select “Gene” * 3. Choose “Search by UV details” * 4. Enter the following details: + Organism Name: Homo sapiens + UV Radiation Type: UVB-radiation + Dose (J/m^2): is less than 100 This will result in 7 entries that match the specified conditions. FAIR Principles Compliance The UVREK database is compliant with the Findable (F), Accessible (A), Interoperable (I), and Reusable (R) data principles (FAIR)^[116]42 which is evident from the following: * (a) It has a stable, permanent web address (F, A). * (b) Entries are uniquely identified by stable URLs (F). * (c) Biomolecules are identified by unique IDs from standardized databases, and corresponding links are provided as detailed in the [117]Methods section (F, I). * (d) References are identified by PMIDs (F, R).