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--**Neurodiagnoses AI** is an open-source, AI-driven framework designed to enhance the diagnosis and prognosis of central nervous system (CNS) disorders. Building upon the Florey Dementia Index (FDI) methodology, it now encompasses a broader spectrum of neurological conditions. The system integrates multimodal data sources—including EEG, neuroimaging, biomarkers, and genetics—and employs machine learning models to deliver explainable, real-time diagnostic insights. A key feature of this framework is the incorporation of the **Generalized Neuro Biomarker Ontology Categorization (Neuromarker)**, which standardizes biomarker classification across all neurodegenerative diseases, facilitating cross-disease AI training.
++=== **Overview** ===
--**Neuromarker: Generalized Biomarker Ontology**
++This section describes the step-by-step process used in the **Neurodiagnoses** project to develop a novel diagnostic framework for neurological diseases. The methodology integrates artificial intelligence (AI), biomedical ontologies, and computational neuroscience to create a structured, interpretable, and scalable diagnostic system.
--Neuromarker extends the Common Alzheimer’s Disease Research Ontology (CADRO) into a comprehensive biomarker categorization framework applicable to all neurodegenerative diseases (NDDs). This ontology enables standardized classification, AI-based feature extraction, and seamless multimodal data integration.
++----
--**Recommended Software**
++=== **1. Data Integration** ===
--There is a suite of software that can help implement the workflow needed in Neurodiagnoses. Find a list of recommendations [[here>>https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/recommended_software]].
++==== **Data Sources** ====
--**Core Biomarker Categories**
++* **Biomedical Ontologies**:
++** Human Phenotype Ontology (HPO) for phenotypic abnormalities.
++** Gene Ontology (GO) for molecular and cellular processes.
++* **Neuroimaging Datasets**:
++** Example: Alzheimer’s Disease Neuroimaging Initiative (ADNI), OpenNeuro.
++* **Clinical and Biomarker Data**:
++** Anonymized clinical reports, molecular biomarkers, and test results.
--Within the Neurodiagnoses AI framework, biomarkers are categorized as follows:
--|=**Category**|=**Description**
--|**Molecular Biomarkers**|Omics-based markers (genomic, transcriptomic, proteomic, metabolomic, lipidomic)
--|**Neuroimaging Biomarkers**|Structural (MRI, CT), Functional (fMRI, PET), Molecular Imaging (tau, amyloid, α-synuclein)
--|**Fluid Biomarkers**|CSF, plasma, blood-based markers for tau, amyloid, α-synuclein, TDP-43, GFAP, NfL, autoantiboides
--|**Neurophysiological Biomarkers**|EEG, MEG, evoked potentials (ERP), sleep-related markers
--|**Digital Biomarkers**|Gait analysis, cognitive/speech biomarkers, wearables data, EHR-based markers
--|**Clinical Phenotypic Markers**|Standardized clinical scores (MMSE, MoCA, CDR, UPDRS, ALSFRS, UHDRS)
--|**Genetic Biomarkers**|Risk alleles (APOE, LRRK2, MAPT, C9orf72, PRNP) and polygenic risk scores
--|**Environmental & Lifestyle Factors**|Toxins, infections, diet, microbiome, comorbidities
++==== **Data Preprocessing** ====
--**Integrating External Databases into Neurodiagnoses**
++1. **Standardization**: Ensure all data sources are normalized to a common format.
++1. **Feature Selection**: Identify relevant features for diagnosis (e.g., biomarkers, imaging scores).
++1. **Data Cleaning**: Handle missing values and remove duplicates.
--To enhance diagnostic precision, Neurodiagnoses AI incorporates data from multiple biomedical and neurological research databases. Researchers can integrate external datasets by following these steps:
++----
--1. (((
--**Register for Access**
++=== **2. AI-Based Analysis** ===
--* Each external database requires individual registration and access approval.
--* Ensure compliance with ethical approvals and data usage agreements before integrating datasets into Neurodiagnoses.
--* Some repositories may require a Data Usage Agreement (DUA) for sensitive medical data.
--)))
--1. (((
--**Download & Prepare Data**
++==== **Model Development** ====
--* Download datasets while adhering to database usage policies.
--* (((
--Ensure files meet Neurodiagnoses format requirements:
++* **Embedding Models**: Use pre-trained models like BioBERT or BioLORD for text data.
++* **Classification Models**:
++** Algorithms: Random Forest, Support Vector Machines (SVM), or neural networks.
++** Purpose: Predict the likelihood of specific neurological conditions based on input data.
--|=**Data Type**|=**Accepted Formats**
--|**Tabular Data**|.csv, .tsv
--|**Neuroimaging**|.nii, .dcm
--|**Genomic Data**|.fasta, .vcf
--|**Clinical Metadata**|.json, .xml
--)))
--* (((
--**Mandatory Fields for Integration**:
++==== **Dimensionality Reduction and Interpretability** ====
--* Subject ID: Unique patient identifier
--* Diagnosis: Standardized disease classification
--* Biomarkers: CSF, plasma, or imaging biomarkers
--* Genetic Data: Whole-genome or exome sequencing
--* Neuroimaging Metadata: MRI/PET acquisition parameters
--)))
--)))
--1. (((
--**Upload Data to Neurodiagnoses**
++* Leverage [[DEIBO>>https://drive.ebrains.eu/f/8d7157708cde4b258db0/]] (Data-driven Embedding Interpretation Based on Ontologies) to connect model dimensions to ontology concepts.
++* Evaluate interpretability using metrics like the Area Under the Interpretability Curve (AUIC).
--* (((
--**Option 1: Upload to EBRAINS Bucket**
++----
--* Location: EBRAINS Neurodiagnoses Bucket
--* Ensure correct metadata tagging before submission.
--)))
--* (((
--**Option 2: Contribute via GitHub Repository**
++=== **3. Diagnostic Framework** ===
--* Location: GitHub Data Repository
--* Create a new folder under /data/ and include a dataset description.
--* For large datasets, contact project administrators before uploading.
--)))
--)))
--1. (((
--**Integrate Data into AI Models**
++==== **Axes of Diagnosis** ====
--* Open Jupyter Notebooks on EBRAINS to run preprocessing scripts.
--* Standardize neuroimaging and biomarker formats using harmonization tools.
--* Utilize machine learning models to handle missing data and feature extraction.
--* Train AI models with newly integrated patient cohorts.
++The framework organizes diagnostic data into three axes:
--**Reference**: See docs/data_processing.md for detailed instructions.
--)))
++1. **Etiology**: Genetic and environmental risk factors.
++1. **Molecular Markers**: Biomarkers such as amyloid-beta, tau, and alpha-synuclein.
++1. **Neuroanatomical Correlations**: Results from neuroimaging (e.g., MRI, PET).
--**AI-Driven Biomarker Categorization**
++==== **Recommendation System** ====
--Neurodiagnoses employs advanced AI models for biomarker classification:
++* Suggests additional tests or biomarkers if gaps are detected in the data.
++* Prioritizes tests based on clinical impact and cost-effectiveness.
--|=**Model Type**|=**Application**
--|**Graph Neural Networks (GNNs)**|Identify shared biomarker pathways across diseases
--|**Contrastive Learning**|Distinguish overlapping vs. unique biomarkers
--|**Multimodal Transformer Models**|Integrate imaging, omics, and clinical data
++----
--**Collaboration & Partnerships**
++=== **4. Computational Workflow** ===
--Neurodiagnoses actively seeks partnerships with data providers to:
++1. **Data Loading**: Import data from storage (Drive or Bucket).
++1. **Feature Engineering**: Generate derived features from the raw data.
++1. **Model Training**:
++1*. Split data into training, validation, and test sets.
++1*. Train models with cross-validation to ensure robustness.
++1. **Evaluation**:
++1*. Metrics: Accuracy, F1-Score, AUIC for interpretability.
++1*. Compare against baseline models and domain benchmarks.
--* Enable API-based data integration for real-time processing.
--* Co-develop harmonized AI-ready datasets with standardized annotations.
--* Secure funding opportunities through joint grant applications.
++----
--**Interested in Partnering?**
++=== **5. Validation** ===
--If you represent a research consortium or database provider, reach out to explore data-sharing agreements.
++==== **Internal Validation** ====
--**Contact**: [[info@neurodiagnoses.com>>mailto:info@neurodiagnoses.com]]
++* Test the system using simulated datasets and known clinical cases.
++* Fine-tune models based on validation results.
--**Final Notes**
++==== **External Validation** ====
--Neurodiagnoses AI is committed to advancing the integration of artificial intelligence in neurodiagnostic processes. By continuously expanding our data ecosystem and incorporating standardized biomarker classifications through the Neuromarker ontology, we aim to enhance cross-disease AI training and improve diagnostic accuracy across neurodegenerative disorders.
++* Collaborate with research institutions and hospitals to test the system in real-world settings.
++* Use anonymized patient data to ensure privacy compliance.
--We encourage researchers and institutions to contribute new datasets and methodologies to further enrich this collaborative platform. Your participation is vital in driving innovation and fostering a deeper understanding of complex neurological conditions.
++----
--**For additional technical documentation and collaboration opportunities:**
++=== **6. Collaborative Development** ===
--* **GitHub Repository:** [[Neurodiagnoses GitHub>>url:https://github.com/neurodiagnoses]]
--* **EBRAINS Collaboration Page:** [[EBRAINS Neurodiagnoses>>url:https://ebrains.eu/collabs/neurodiagnoses]]
++The project is open to contributions from researchers, clinicians, and developers. Key tools include:
--If you encounter any issues during data integration or have suggestions for improvement, please open a GitHub Issue or consult the EBRAINS Neurodiagnoses Forum. Together, we can advance the field of neurodiagnostics and contribute to better patient outcomes.
++* **Jupyter Notebooks**: For data analysis and pipeline development.
++** Example: [[probabilistic imputation>>https://drive.ebrains.eu/f/4f69ab52f7734ef48217/]]
++* **Wiki Pages**: For documenting methods and results.
++* **Drive and Bucket**: For sharing code, data, and outputs.
++* **Related projects: **For instance: [[//Beyond the hype: AI in dementia – from early risk detection to disease treatment//>>https://www.lethe-project.eu/beyond-the-hype-ai-in-dementia-from-early-risk-detection-to-disease-treatment/]]
++
++----
++
++=== **7. Tools and Technologies** ===
++
++* **Programming Languages**: Python for AI and data processing.
++* **Frameworks**:
++** TensorFlow and PyTorch for machine learning.
++** Flask or FastAPI for backend services.
++* **Visualization**: Plotly and Matplotlib for interactive and static visualizations.
++* **EBRAINS Services**:
++** Collaboratory Lab for running Notebooks.
++** Buckets for storing large datasets.

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