Alzheimer's Disease Precision Medical Data Research Platform Construction And Application

Objective:Through data standard unified and specification of data upload process, individual factors, environmental factors, genetic factors, body fluids, biomarkers, neuropsychological and neuroimaging data and omics data are fully integrated. Many indicators associated with alzheimer disease (AD) are filtrated, such as China's aging population, environment, genetic selection, humoral markers, image markers, and neuropsychological assessment. Based on standard specification, resource sharing and efficient use, AD precision medical data research platform are established to build a multidimensional AD risk prediction model, research and develop AD precision (individualized) technology system, explore the AD early diagnosis and prediction system, change the network (or pathway) mechanism and early intervention of new targets, and provide the basis for big data and open innovation research platform.Methods:1. Large sample AD queue and follow-up data are gathered:Infrastructure construct including united application and supported platform, server and virtualization, storage and backup, the integration of security and data center unified management. Therefore, the centralized storage and management of AD data are realized to support cross-regional medical business; Software platform construction mainly includes the storage hardware, analysis hardware, analysis software, mining software and application software. A parallel computing framework based on Hadoop data parallel processing and mining platform is provided; Specific system architecture are B/S structure, J2EE framework of SSH framework technology and business points module in design concept, mainly including the business layer, function layer, platform layer and base layer.2. The key risk factor for Alzheimer disease (AD) are gathered:genetic factors mainly include amyloid precursor protein (APP), early old element 1 gene (PS1), the old element 2 (PS2) gene mutation detection and apolipoprotein E (ApoE) gene subtype gene detection; Personal basic factors mainly include the basic situation, life behavior, dietary structure and nutrition status, social support and social negative event, past medical history, present medical history, vascular risk factors, occupational exposure, physical examination and auxiliary examination, etc. Environmental factors mainly include life history, living environment, occupation and job performance, etc; Humoral factors mainly include blood routine, blood fat, liver meritorious and biochemical, five items of blood clotting, urine routine, stool routine, virus series, thyroid function, vitamin B12, folic acid, carcinoembryonic antigen, syphilis antibodies, HIV antibodies, blood type A ? 40, blood type A ?42, blood protein tau beta, IL-1 ?, TNF-?, IL-6, urine AD relevant neurofilament protein (AD7c-NTP) and cerebrospinal fluid A ? 40, A ? 42, total protein(T-tau), phosphorylation protein (p-tau), specific loci (including p-tau231, p-tau181); Neuropsychological mainly include memory disorders since the rating scale (AD8), simple mental state scale (MMSE), memory, and perform screening scale (MES), Montreal cognitive assessment scale (MoCA), complete sets of cognitive function test (word fluency, Boston named, FOM, the Chinese version of learning tests-12 words, words, learn the training test-delayed recall, words recognition, digit span, track test, and draw the clock test) and neuropsychological scale-record (NPI) (ask families or person), daily life ability scale (ADL), clinical dementia rating scale (CDR), Hachinski ischemia scale (ihs), geriatric depression scale (GDS), Hamilton's depression scale (HAMD), apathy symptom rating scale (AES), IQCODE, caregivers self-efficacy questionnaire; Neuroimaging includes cerebral MRI scan, diffusion weighted imaging (DWI) can, magnetic sensitive weighted imaging (SWI), diffusion tensor imaging (DTI), determination of hippocampal volume,magnetic resonance spectroscopy (1H-MRS),functional MRI (fMRI), electroencephalogram (EEG) and multimodal magnetic resonance imaging, etc.; Diagnosis, treatment and follow-up data mainly include symptoms and complaints, hpi, internal medicine and neurology specialized physical examination results, other medical history, history of drug use and trauma history, etc. Follow-up content were the same as baseline survey, including questionnaires, complete sets of neuropsychological assessment, diagnosis and treatment effect for patient, treatment (including drugs, treatment time and treatment effect, etc.), outcome prognosis, and biological samples are gathered. Active follow-up and disease surveillance network are combined. At the same time of actively follow-up, the crowd disease surveillance network (mortality surveillance system, slow disease risk factor surveillance system, health care system, the hospital electronic medical record system, regional health information system, etc.) are used, dynamic tracking information of benign and malignant disease and treatment related to AD, and transfer, treatment and survival status.3. AD biological samples resources data is gathered:preparation of biological specimens (cerebrospinal fluid, blood, urine, saliva, etc.) collection, transportation, storage process, establish a library of biological specimens; Operation procedures of the biological specimens such as management, search, separation, repackaging are standardize. Specimens are cryopreserved in-80? refrigerator and scientifically coded. Throughout the specimen processing, attention should be paid to avoid sample degradation and pollution. After filling the details of transfer list, specimens of different ground are transfered on the cold chain of transport process and adjusted according to the specimen transportation time, distance, weather, seasons, methods, types and volume of sample. In the process of transport packaging, specimens are isolated with appropriate materials and enough amount of refrigerant are use to ensure the refrigeration conditions of the transit.4. AD precision medical standardized is researched:the content of the standardization system includes standardized diagnosis, standardized process, standardized data, standardized management and standardized technical; Supporting function for the construction of standard system mainly refers to the AD data exchange standard including baseline core standards, data format of metadata and data exchange protocol, development interface test module, and interoperability and consistency test; AD service data and privacy protection standards, service credible test module, the platform level of privacy protection, transparency and trust level evaluation are all developed; AD data performance test standard, big data development performance test module, and the relevant test systems and platforms are also carried out.5. A variety of measures to ensure the security of the huge amounts of data:the safety evaluation of key technologies are researched. Safety evaluation system is set up. with the help of a safety evaluation tools, safety evaluation platform is set up covering the AD data, medical cloud computing and medical application to realize the AD data comprehensive security test validation. Many aspects of security such as the patients privacy protection, data safety protection, safety management system, data transmission security are done well.Results:1. AD precision medical big data research platform:Multicenter AD cases registration system and its network transmission system is developed, which gathers basic information of AD cases, clinical information, image information, laboratory tests, treatment and medication information, biological samples information and follow-up information of patients into the group every hospitals through the hospital electronic medical record (EMR), a medical information system (PEIS), medical image archiving and communication system (PACS), the laboratory information system (LIS), the outpatient service system and the hospital system by means of network resource advantage of Shandong Province telemedicine center. All information are imported in real time to the two-dimensional structured database, which is connected automatically to the biological specimen omics database (genomics, metabolomics, epigenetic omics, etc.), to realize automation, network and real-time of acquisition and tracking of the follow-up cohort information and meet a variety of operating systems of remote data access. Medical data and biological samples data platform, follow-up data platform and health data platform are constructed.2. Applications of AD precision medical data research platform:AD epidemiology network system is established. AD etiology epidemiological studies are carried out to explore epidemiological characteristics, distribution and rule and to provide theoretical basis of AD to public health policy. AD precision medical statistics and analysis system is set up, including AD precision medical research design and statistical analysis method system, AD precision medical technology platform based on clinical study large data set and large data system based on the statistical analysis; AD early diagnosis and risk prediction system is established, including early warning system and early recognition and risk prediction model; Interdisciplinary, cross major, many fields of AD data integration platform is set up, whose data is centralized stored in Shandong Province AD data center to achieve the sharing and exchange of AD medical health data; AD network system of the remote collaboration diagnosis and treatment and regional tertiary hospitals cross-regional, across different hospitals, specialized subject of AD multidisciplinary comprehensive diagnosis and treatment of knotty disorder (AD-MDT) service platform are established to improve the quality in remote areas at the grass-roots level to extension AD the accessibility of medical service; AD network hospital is set up to form regional cooperative medical service system (health management, difficult-and-rare-case consultation, referral courtyard, appointment diagnosis and treatment, mobile health care and home care, etc.).3. AD standardization research and knowledge database:AD data standardization is researched. National multicenter AD precision medical research platform form unified AD standard system on the basis of construction standard, unified business process, data definition and coding, a unified data exchange standard including basic standards, data standard, specification, management standards and business practices. AD precision medical related technical and diagnosis standard are established such as the basic information, clinical diagnosis and clinical treatment carried on the standardization. The data dictionary uses the state, local and industry standards to maximize the elimination of heterogeneous data due to name, description, classification and coding of information to ensure that transmission and exchange of information between different hospitals information system are consist to improve processing speed of information; Based on the accurate chain data of the AD accurate medical knowledge base is constructed. Wear equipment data includes the blood pressure, blood glucose, pulse, heart rate, blood oxygen content, temperature and dynamic monitoring data such as BMI. Health records data includes basic information, family history, disease history, physical examination, the living environment, living habits, etc. Medical health data includes signs and symptoms, biochemical examination, imaging and pathological examination, treatment, etc. Biological samples data mainly refers to genomics, proteomics, proteomics and metabolomics transcription. Follow-up data includes clinical effects, medication situation and prognosis of outcome data. Based on the above one-to-one AD accurate data, score is quantified and AD precision medical global database is eventually formed.Conclusions:This study has established the AD precision medical data research platform through integrating individual factors, environmental factors, genetic factors, body fluids, biomarkers, neuropsychological and neuroimaging data and omics data to build multidimensional AD risk prediction model with time evolution characteristics. It can realize early warning of disease risk to provide technical support, basic data and open innovation research platform for medical and health management services. The next step is that through the data mining, processing and modeling, individuals at risk for the elderly AD can be early screened, identificated and disease risk predicted to achieve early detection and treatment, make the quality of life and prognosis of patients better, improve the control level of regional AD and promote brain health of elderly population earlier and better. At the same time, the development of AD relevant genetics and serology etiology study can also provide clues for research on etiology and mechanism of AD and provide theoretical basis for further research on early brain disease prevention and control of precision technology.