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ournal of Infection and Public Health (2016) 9, 331—338

uman Disease Insight: An integratednowledge-based platform forisease-gene-drug information

unazzah Tasleem, Romana Ishrat, Asimul Islam,aizan Ahmad, Md. Imtaiyaz Hassan ∗

entre for Interdisciplinary Research In Basic Sciences, Jamia Millia Islamia,amia Nagar, New Delhi 110025, India

eceived 5 April 2015; received in revised form 21 May 2015; accepted 23 October 2015

KEYWORDSHuman diseasedatabase;Human genomeproject;Data integration;Knowledgemanagement system;Relational databasemanagement system

Summary The scope of the Human Disease Insight (HDI) database is not limited toresearchers or physicians as it also provides basic information to non-professionalsand creates disease awareness, thereby reducing the chances of patient suffer-ing due to ignorance. HDI is a knowledge-based resource providing information onhuman diseases to both scientists and the general public. Here, our mission is toprovide a comprehensive human disease database containing most of the availableuseful information, with extensive cross-referencing. HDI is a knowledge manage-ment system that acts as a central hub to access information about human diseasesand associated drugs and genes. In addition, HDI contains well-classified bioinfor-matics tools with helpful descriptions. These integrated bioinformatics tools enableresearchers to annotate disease-specific genes and perform protein analysis, searchfor biomarkers and identify potential vaccine candidates. Eventually, these toolswill facilitate the analysis of disease-associated data. The HDI provides two types ofsearch capabilities and includes provisions for downloading, uploading and searchingdisease/gene/drug-related information. The logistical design of the HDI allows for

regular updating. The database is designed to work best with Mozilla Firefox andGoogle Chrome and is freely accessible at http://humandiseaseinsight.com.© 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by ElsevierLimited. All rights reserved.

∗ Corresponding author. Tel.: +91 11 2698 3409;ax: +91 11 2698 3409; mobile: +91 9990323217.

E-mail address: imtiyaz.hassan@gmail.com (Md.I. Hassan).

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ttp://dx.doi.org/10.1016/j.jiph.2015.10.018876-0341/© 2015 King Saud Bin Abdulaziz University for Health Scie

ntroduction

cientists have documented diseases within spe-ific categories in various online databases. Due todvancements in science and technology, especially

nces. Published by Elsevier Limited. All rights reserved.

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in genomics and information technology, we haveentered in an exciting era of modern biology. Themajor challenge that the medical science commu-nity is presently facing is the integration of vastand rapidly growing amounts of information on vari-ous diseases into a holistic understanding. Recently,there has been considerable progress in diseasegenetics and genome-related medicine, leading tothe generation of extensive data. The remarkableapproach adopted by the Human Genome Project[1,2] making human genome, transcriptome andproteome data publicly available through onlinedatabases has facilitated in-depth investigations ofdisease genetics.

Currently, databases containing informationabout human diseases are focused predomi-nantly on a particular disease category, suchas all known Mendelian disorders describedin the Online Mendelian Inheritance in Man(OMIM) [3]; infectious disease information,such as that found in the Infectious DiseaseBiomarker Database [4]; rare childhood diseases(http://www.madisonsfoundation.org/index.php);hereditary ocular diseases (https://disorders.eyes.arizona.edu); dermatological diseases (http://www.aocd.org/); and gastrointestinal diseases(http://www.gastro.net.au/). Other databases,such as the Malaysian National CardiovascularDisease Database (NCVD), give an overview ofcardiovascular disease and maintain records ofpatients suffering from these diseases [5]. In addi-tion, the Indian Genetic Disease Database (IGDD) isa mutation data repository for genetic diseases inIndia; however, the information stored in the IGDDis helpful only to researchers [6]. Another databasethat provides information about autoimmune dis-orders is the Autoimmune Disease Database, whichgives descriptions of autoimmune disorders andlinks these diseases to candidate genes, which is,again, a database that useful only for researchers[7]. The Comparative Toxicogenomic Database(CTD) is a rich resource for researchers to accessinformation about the etiology of environmentaldiseases and explore chemical-gene and proteininteractions [8]. Such attempts have contributedenormously to efforts related to the prevention,diagnosis and treatment of diseases and haveresulted in the development of new approachesto alleviate the consequences of life-threateningillnesses. However, no disease database providingguidance related to bioinformatics tools and infor-mation available to members of the non-scientific

public currently exists. Hence, the integration ofinformation on all human diseases from differentcategories within a common place has become animportant issue in the field of bioinformatics.

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In recent years, the scientific community haseen able to gain information through a num-er of useful internet-accessible resources, inddition to text books of biological and medicalnformation. In the database development field,nternet-accessible information retrieval systemsave recently become popular due to the reducedosts of data storage and transfer. Vast amountsf biomedical information can be accessed throughhe World-Wide Web (WWW), although this infor-ation is scattered. Additionally, the heterogeneity

nd complexity of the available resources meanshat some information cannot be retrieved in aimely fashion. Furthermore, the rapidly growingelds related to disease information, genomics androteomics databases and drug discovery and thexpeditious development of computational toolso solve biological queries necessitate the inte-ration of all of these information sources in aell-organized and concise database. Over a periodf time, advancements in diagnostic evaluation andreatment have emerged. To provide the commu-ity with the most recent knowledge on humaniseases and the discovery of genes involved iniseases, we have created a Knowledge Manage-ent System (KMS) that includes information on

arious categories of human diseases, the drugssed to cure these diseases, and the genes involvedn causing these diseases, as well as bioinfor-atics tools for analyzing the genes in question.he HDI is therefore a comprehensive databasef human diseases belonging to various categorieshat is cross-linked to other databases to retrieveetailed information on genes, drugs and tools.he HDI exhibits broad utility as it renders clini-al information for physicians, genetic informationnd tool classification for researchers and diseaseescriptions for the general public. Thus, the HDIims to provide a better understanding of humaniseases, genes and drugs, as well as their relation-hips with one another, and allows easy retrievalf information through its user-friendly web-basedpplications.

aterials and methods

verview of the database, HDI

he Human Disease Insight (HDI) database intro-uces an integrated knowledge base of diseases,enes and drugs and a list of bioinformatics tools

ith a user-friendly interface. The databaseas developed to allow simple retrieval of dis-ase/gene/drug information and exploratorynalysis of disease-specific genes within a single

Human Disease Insight 333

Table 1 Summary of the raw data included in the HDI.

Sections Entries Numbers

Diseases

Diseases of the Circulatory System 24Diseases of the Digestive System 14Diseases of the Eye and Adenexa 41Diseases of the Musculoskeletal System 15Disease of the Genitourinary System 15Diseases of the Respiratory System 16Diseases of the Skin and Subcutaneous Tissues 08Disorders of the Perinatal Period 05Endocrine, Nutritional and Metabolic Diseases 216Hematological Disorders 59Infectious Diseases 145Malignant Neoplasms 67

Drugs

Anesthetics 16Anti-infective Medications 56Anti-allergics and Medicines used in Anaphylaxis 8Antidotes 14Anti-epileptic Drugs 7Anti-migraine Medicines 4Antineoplastic and Immunosuppressive 41Anti-parkinsonism Medicines 02Blood products and Plasma substitutes 10Cardiovascular Medicines 28Dermatological Medicines 17Diagnostic Agents 10Disinfectants and Antiseptics 13Diuretics 4Gastrointestinal Medicines 18Hormones and Endocrine Medicines 22Immunologics 13Medicines Acting on the Respiratory Tract 06Medicines Affecting Blood 10Muscle Relaxants and Cholinesterase Inhibitors 05NSAIDs and Antipyretics—Analgesics 13Ophthalmological Preparations 17Oxytocics and Antioxytocics 07Psychotherapeutic Medicines 11Solutions Correcting Water, Electrolyte and Acid-base 09Vitamins and Minerals 09

Genes 1440

Tools

DNA Sequence Analysis 33Genomics 05Modeling 09

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ocation. It is designed to assemble, store, organizend display information about human diseases,enes associated with human diseases and drugssed to cure diseases in conjunction with a clas-ified list of bioinformatics tools for sequencenalysis and structural protein modeling. TheDI currently contains information on 625 human

iseases, 320 drugs, 1440 genes and a classified listf bioinformatics tools (see Table 1). The diseasesave been classified into 12 categories, and each

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ategory has been populated with disease informa-ion that includes synonym(s), pathogens, generalisease descriptions, genes, clinical features,athways, investigations, prevention, treat-ents, risk factors, prevalences and references

9—11] (http://www.nlm.nih.gov/medlineplus/,ttp://www.medscape.com/). Drugs have been

lassified into 26 broad categories [12]. The assign-ent of genes to human diseases includes links to

he National Center for Biotechnology Information

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(NCBI) [13] and the Universal Protein Resource(UniProt) [14] databases for detailed information.Bioinformatics tools are broadly classified into4 main categories, and each category is thencategorized into further sub-categories [15]. Eachentry in the list of tools provides a brief descriptionand an external link. Information collected fordiseases, drugs and genes is interconnected insuch a way that (i) through the disease option,multiple genes and/or multiple drugs involved ina particular disease can be retrieved; (ii) throughthe drugs option, the number of diseases for whicha particular drug can be used is retrieved; and (iii)through the gene option, the number of disease(s)with which a particular gene is associated canbe displayed. These pieces of information can beaccessed freely. The information available in theHDI is derived from various resources, includingelectronic media, articles published in PubMed andtext books and is curated and updated regularly.

Database structure

The HDI is a knowledge-based data warehouse thatprovides an integrated and curated repository ofhuman diseases and related information. The clas-sification of bioinformatics tools, together withdescriptions of and links to their respective webpages, assists in performing research analyses ofgene/protein sequences. The HDI provides a user-friendly web interface to allow the user to retrieve,download and upload information through interac-tive web forms. A schematic representation of thelogistics used in the HDI is shown in Fig. 1

Software design and implementation

The HDI data warehouse was developed andis executed based on a three-tier architecture-user/client web-interface and a relational databasemanagement system (RDBMS) at the backend. Theuser/client can be a physician, researcher, stu-dent and/or member of the general public. Theweb interface is composed of web pages and webforms, designed in HTML5, CSS, PHP, JavaScript,ajax, jquery and MySql queries, to provide a com-mon gateway interface. At the backend, we havecreated data marts to persistently and securelystore information pertaining to human diseases.This database has been dynamically constructed,and web pages and web forms are interlinked withthe data warehouse created at the backend for

querying the database as instructed by the end userthrough button clicks and drop-down menus. Thedata warehouse created at the backend is a rela-tional database managed by MySql and developed

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n the Windows operating system. For web ser-ices, the Apache HTTP web server is used. Dataining was performed to retrieve information on

uman diseases, genes, drugs and tools througharious web resources and text books. The datahus obtained were then subjected to curation andploaded to the database.

The framework for the HDI primarily consists ofables containing information on diseases, drugsnd genes together with bioinformatics tools. Eachisease category is populated with a number of dis-ases. Each entry in HDI provides comprehensivenformation about a human disease, characterizedy its synonym(s), general description, pathogen,nvolved genes, clinical features, pathways, inves-igations, prevention, treatment, related drugs,revalence, risk factors and associated references.ach drug category is populated with a number ofrugs together with descriptions and links to drugatabanks for detailed information. Genes involvedn human diseases are collected, and related linkso NCBI and UniProt are provided in a drop-downenu to retrieve detailed knowledge. For user con-

enience, major bioinformatics tools, together withheir descriptions and links, are classified in anffort to provide guidance for performing specifiednalyses of genes/proteins. The HDI can be freelyccessed from any web browser.

ata curation

nformation is stored in the HDI after extensive lit-rature, web and text-mining, followed by datauration. The HDI is being enhanced through con-inued efforts to improve disease knowledge andhe interlinking of disease, drug and gene tableso obtain optimum information. The informations made available to the user after an extensiveata-mining process. The knowledge thus obtaineds managed in a relational database through cross-inking to fetch the data stored in the HDI dataarehouse and via cross-linking of web resources

NCBI, UniProt and DrugBank). Genes related touman diseases are included in the database andre interlinked with disease tables to obtain theame(s) of disease(s) governed by a specific gene.

nowledgebase access

DI data can be retrieved efficiently through therop-down menus and search functions provided onach page of the web site. The user can access

lphabetically ordered diseases, drugs, genes andools through a drop-down menu. Diseases fromifferent categories can be selected through arop-down menu. Clicking on ‘‘Disease’’ displays

Human Disease Insight 335

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ome of the stored information about the dis-ase, together with a ‘‘More’’ button. Clicking onhe ‘‘More’’ button leads to detailed informationbout the selected disease. Similarly, drugs cane selected from different categories in the drop-own menu; clicking on any drug will provide itsescription, disease(s) that can be cured by therug and links to a drug bank for details. In the sameanner, a gene of interest can be selected from

he drop-down menu, which will display a table

ith links to NCBI and UniProt to provide detailed

nformation and the names of diseases causedy mutations in the gene. Two different searchoxes are provided for user convenience. We have

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f data entry and retrieval in HDI.

ncorporated three search boxes on the home pagehat can be used to search the complete data martor diseases, drugs and genes individually in the HDIata warehouse. To enhance the usability of theseearch boxes, codes were written to provide auto-omplete search suggestions to the user, which willeduce search time and correct spelling errors. Anxample showing a working model of the searchox is shown in Fig. 2 (Supplementary Figs. 1—5,escribing the main web pages of the HDI). Another

earch included on each page is a Google search boxhat searches for the entered term in the database,s well as on the web. Our web site includes arovision for downloading and uploading published

336 M. Tasleem et al.

Figure 2 An example of using the HDI search box. (a) Disease search box showing suggestions for selecting the desiredr. (b

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disease for retrieving information by typing only one lettedisease of interest.

articles, e-books and articles related to diseases,drugs and genes for registered users. All uploadsfrom users will be updated in the database in atimely manner. For registration, a signup optionis provided, and a registered user can login todownload and upload related information. Medic-inal and research-oriented news will be e-mailedto the provided by the user. A user feedback optionis provided to improve the database. An advertise-ment option is provided for advertising companiesto display their advertisements in the space of theweb site after filling in the form. Furthermore, thedatabase is connected to social networking sites toincrease its popularity.

Results and discussion

Database availability

The database can be accessed free of charge toretrieve data on diseases, drugs and genes, as wellas tool-related information. Free registration isrequired to download and upload related content.

Salient features of the HDI

The HDI is a robust knowledge management sys-tem that manages data-mined knowledge throughcross-linking of data marts and web resources. Thisuser-friendly, data-intensive repository providesthe user with a platform to retrieve compre-hensive disease-related information and perform

gene/protein sequence-based analyses using directlinks to classified bioinformatics tools. The HDIallows users to upload content to improve thedatabase.

adn

) Information retrieval page accessed after selecting the

omparison with other available diseaseatabases

he HDI is a unique human disease databaseecause although there are a number of existingatabases that provide information for a particu-ar category of disease; however, these databasesre useful only for clinicians or researchers. Somef the existing disease databases include PedBase,he Online Mendelian Inheritance in Man (OMIM)atabase, the Indian Genetic Disease Database,he Global Infectious Diseases and Epidemiologyetwork (GIDEON), the Office of Rare Diseasesesearch (ORDR) database, the Dermatologic Dis-ase Database, NeuroDnet and CADgene. PedBasehttp://www.pedbase.org/) is a pediatric diseaseatabase that provides information related to child-ood diseases that is only for clinicians. The OMIMatabase is a comprehensive database that pro-ides knowledge related to human genetic disorders3]. The Indian Genetic Disease Database is aatabase that provides information on mutationsn causal genes for genetic diseases that are com-on in India [6]. The Global Infectious Diseases

nd Epidemiology Network (GIDEON) presents rel-vant information about infectious diseases andheir epidemiology [16]. The Office of Rare Diseasesesearch (ORDR) database is a database registry forare diseases and disorders linked to biorepositories17]. The Dermatologic Disease Database (http://ww.aocd.org/?page=DiseaseDatabaseHome) pro-ides information regarding skin diseases. NeuroD-et is a database that provides relevant informationbout signaling molecules, genes and proteins andheir interactions for constructing neurodegener-

tive disease networks [18]. CADgene providesetailed information on genes related to coro-ary artery diseases and tools to construct gene

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etworks but does not provide any informationbout the disease caused by the gene of interest19].

Multiple databases have been created to addressroblems related to specific disease categories,hich highlights the importance of compiling

nformation on all human diseases from variousategories under a common platform for analy-is. This issue has been resolved by the creationf the HDI, which contains relevant informationbout human diseases from various categories,long with descriptions and cross-references of theenes involved and the drugs used to treat them.his database contains a well-classified list of com-utational tools, along with descriptions of theseools and links to their sources. The distinct char-cteristic of the HDI is the inclusion of informationn genes, drugs and tools to aid in the explorationf human diseases. Additionally, a word-suggestingearch engine for searching diseases/genes andrugs is provided. The HDI allows users to down-oad and upload relevant content. The data in theDI are updated regularly. The purpose of devel-ping the HDI was to provide a simple solution tollow physicians, researchers and non-professionalso extract information on human diseases, genes,rugs and bioinformatics. The extensively cross-eferenced, unified information provided, togetherith the facility of downloading and uploadingontent in a user-friendly manner, make the HDInique. Thus, the concept of HDI is different fromhat of other available disease databases.

uture directions

he HDI provides optimum information requiredor the diagnosis and treatment of various humaniseases. There are currently 625 diseases, 1440enes, 320 drugs and 82 tools in the HDI. Thenformation available in specific fields is rapidlyxpanding. Our aim is to collect a complete datasetor human diseases, genes, drugs and tools ando generate an integrated platform that can bemployed to identify genes causing human disease.e also aim to integrate various bioinformatics

ools to annotate human disease-specific genes. Inhe future, the main challenge will be to maintainn up-to-date dataset with the growing number dis-ases, genes, drugs and bioinformatics tools.

onclusion

he HDI offers a premier platform that addressesll aspects of diseases, including their history,

337

ymptoms, causes, epidemiology, treatment, pre-autions, etc. Moreover, all diseases have beeninked with data regarding their pharmacology andenomics and proteomics, as well as many other rel-vant databases. The HDI will not only contributeo a greater understanding of disease and providerimary data for research but will also enable thedentification of interactions among various dis-ases through comparisons conducted with variousools provided in our database. The informationrovided by the HDI will lay the foundation forurther advances in disease diagnosis and aid inhe design of novel approaches for diagnosing andreating diseases. We believe that with the enrich-ent of the database, users will be able to access

nformation about all human diseases.Availability: This database is available at:

ttp://www.humandiseaseinsight.com.

unding

he HDI is supported by grants from the Universityrants Commission (UGC) [F. No. 40-201/2011(SR)].

ompeting interests

one declared.

thical approval

ot required.

cknowledgement

he authors thank the FKT-Center for Informationechnology (Jamia Millia Islamia, New Delhi, India)or providing technical support.

ppendix A. Supplementary data

upplementary data associated with this article cane found, in the online version, at http://dx.doi.rg/10.1016/j.jiph.2015.10.018.

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