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... ... @@ -1,207 +1,260 @@ 1 -** # Neurodiagnoses AI: Multimodal AI for Neurodiagnostic Predictions**1 +== **Overview** == 2 2 3 -## **Project Overview** 4 -Neurodiagnoses AI implements AI-driven diagnostic and prognostic models for central nervous system (CNS) disorders, adapting the Florey Dementia Index (FDI) methodology to a broader set of neurological conditions. The approach integrates **multimodal data sources** (EEG, neuroimaging, biomarkers, and genetics) and employs **machine learning models** to provide **explainable, real-time diagnostic insights**.## 3 +This project develops a **tridimensional diagnostic framework** for **CNS diseases**, incorporating **AI-powered annotation tools** to improve **interpretability, standardization, and clinical utility**. The methodology integrates **multi-modal data**, including **genetic, neuroimaging, neurophysiological, and biomarker datasets**, and applies **machine learning models** to generate **structured, explainable diagnostic outputs**. 5 5 6 -## **How to Use External Databases in Neurodiagnoses** 7 -To enhance diagnostic accuracy, Neurodiagnoses integrates data from multiple biomedical and neurological research databases. Researchers can follow these steps to access, prepare, and integrate data into the Neurodiagnoses framework.## 5 +== **Workflow** == 8 8 9 - ###**Potential Data Sources**10 - Neurodiagnosesmaintains anupdated listfpotentialbiomedicaldatabasesrelevant to neurodegenerativediseases. ##7 +1. ((( 8 +**We Use GitHub to [[Store and develop AI models, scripts, and annotation pipelines.>>https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/discussions]]** 11 11 12 -**Reference: List of Potential Databases** 13 -- **ADNI**: Alzheimer's Disease data ([ADNI](https://adni.loni.usc.edu)) 14 -- **PPMI**: Parkinson’s Disease Imaging and biospecimens ([PPMI](https://www.ppmi-info.org)) 15 -- **GP2**: Whole-genome sequencing for PD ([GP2](https://gp2.org)) 16 -- **Enroll-HD**: Huntington’s Disease Clinical and genetic data ([Enroll-HD](https://www.enroll-hd.org)) 17 -- **GAAIN**: Multi-source Alzheimer’s data aggregation ([GAAIN](https://gaain.org)) 18 -- **UK Biobank**: Population-wide genetic, imaging, and health records ([UK Biobank](https://www.ukbiobank.ac.uk)) 19 -- **DPUK**: Dementia and Aging data ([DPUK](https://www.dementiasplatform.uk)) 20 -- **PRION Registry**: Prion Diseases clinical and genetic data ([PRION Registry](https://prionregistry.org)) 21 -- **DECIPHER**: Rare genetic disorder genomic variants ([DECIPHER](https://decipher.sanger.ac.uk)) 10 +* Create a **GitHub repository** for AI scripts and models. 11 +* Use **GitHub Projects** to manage research milestones. 12 +))) 13 +1. ((( 14 +**We Use EBRAINS for Data & Collaboration** 22 22 23 - ###**1.RegisterforAccess**24 - -Eachexternaldatabaserequires**individualregistration**andaccessapproval.25 - -Ensurecompliancewith**ethicalapprovals**and **datausage agreements**beforeintegratingdatasets intoNeurodiagnoses.26 - - Some repositories may require a **Data Usage Agreement (DUA)** for sensitive medical data.##16 +* Store **biomarker and neuroimaging data** in **EBRAINS Buckets**. 17 +* Run **Jupyter Notebooks** in **EBRAINS Lab** to test AI models. 18 +* Use **EBRAINS Wiki** for structured documentation and research discussion. 19 +))) 27 27 28 -### **2. Download & Prepare Data** 29 -- Download datasets while adhering to database usage policies. 30 -- Ensure files meet **Neurodiagnoses format requirements**: 31 - - **Tabular Data**: `.csv`, `.tsv` 32 - - **Neuroimaging Data**: `.nii`, `.dcm` 33 - - **Genomic Data**: `.fasta`, `.vcf` 34 - - **Clinical Metadata**: `.json`, `.xml`## 21 +---- 35 35 36 -- **Mandatory Fields for Integration**: 37 - - **Subject ID**: Unique patient identifier 38 - - **Diagnosis**: Standardized disease classification 39 - - **Biomarkers**: CSF, plasma, or imaging biomarkers 40 - - **Genetic Data**: Whole-genome or exome sequencing 41 - - **Neuroimaging Metadata**: MRI/PET acquisition parameters 23 +== **1. Data Integration** == 42 42 43 -### **3. Upload Data to Neurodiagnoses** 44 -**Option 1: Upload to EBRAINS Bucket** 45 -- Location: **EBRAINS Neurodiagnoses Bucket** 46 -- Ensure correct **metadata tagging** before submission.## 25 +=== **EBRAINS Medical Informatics Platform (MIP)**. === 47 47 48 - **Option 2: Contribute via GitHub Repository** 49 -- Location: **GitHub Data Repository** 50 -- Create a new folder under `/data/` and include a **dataset description**. 51 -- For large datasets, contact project administrators before uploading. 27 +Neurodiagnoses integrates clinical data via the **EBRAINS Medical Informatics Platform (MIP)**. MIP federates decentralized clinical data, allowing Neurodiagnoses to securely access and process sensitive information for AI-based diagnostics. 52 52 53 -### **4. Integrate Data into AI Models** 54 -- Open **Jupyter Notebooks** on EBRAINS to run **preprocessing scripts**. 55 -- Standardize **neuroimaging and biomarker formats** using harmonization tools. 56 -- Use **machine learning models** to handle missing data and feature extraction. 57 -- Train AI models with **newly integrated patient cohorts**.## 29 +==== How It Works ==== 58 58 59 -**Reference**: See `docs/data_processing.md` for detailed instructions. 60 60 61 -## **Collaboration & Partnerships**## 62 -# **Partnering with Data Providers** 63 -Neurodiagnoses seeks partnerships with data repositories to: 64 -- Enable **API-based data integration** for real-time processing. 65 -- Co-develop **harmonized AI-ready datasets** with standardized annotations. 66 -- Secure **funding opportunities** through joint grant applications. 32 +1. ((( 33 +**Authentication & API Access:** 67 67 68 -**Interested in Partnering?** 69 -- If you represent a research consortium or database provider, reach out to explore data-sharing agreements. 70 -- **Contact**: info@neurodiagnoses.com 35 +* Users must have an **EBRAINS account**. 36 +* Neurodiagnoses uses **secure API endpoints** to fetch clinical data (e.g., from the **Federation for Dementia**). 37 +))) 38 +1. ((( 39 +**Data Mapping & Harmonization:** 71 71 72 -## **Final Notes** 73 -Neurodiagnoses continuously expands its data ecosystem to support AI-driven clinical decision-making. Researchers and institutions are encouraged to contribute **new datasets and methodologies**.## 41 +* Retrieved data is **normalized** and converted to standard formats (.csv, .json). 42 +* Data from **multiple sources** is harmonized to ensure consistency for AI processing. 43 +))) 44 +1. ((( 45 +**Security & Compliance:** 74 74 75 -For additional technical documentation: 76 -- **GitHub Repository**: [Neurodiagnoses GitHub](https://github.com/neurodiagnoses) 77 -- **EBRAINS Collaboration Page**: [EBRAINS Neurodiagnoses](https://ebrains.eu/collabs/neurodiagnoses) 47 +* All data access is **logged and monitored**. 48 +* Data remains on **MIP servers** using **federated learning techniques** when possible. 49 +* Access is granted only after signing a **Data Usage Agreement (DUA)**. 50 +))) 78 78 79 - Ifyou experience issues integrating data, **opena GitHub Issue** or consultthe **EBRAINS Neurodiagnoses Forum**.52 +==== Implementation Steps ==== 80 80 81 -== **How to Use External Databases in Neurodiagnoses** == 82 82 83 -To enhance the accuracy of our diagnostic models, Neurodiagnoses integrates data from multiple biomedical and neurological research databases. If you are a researcher, follow these steps to access, prepare, and integrate data into the Neurodiagnoses framework. 55 +1. Clone the repository. 56 +1. Configure your **EBRAINS API credentials** in mip_integration.py. 57 +1. Run the script to **download and harmonize clinical data**. 58 +1. Process the data for **AI model training**. 84 84 85 - ===**Potential DataSources**===60 +For more detailed instructions, please refer to the **[[MIP Documentation>>url:https://mip.ebrains.eu/]]**. 86 86 87 - Neurodiagnoses maintains an updated list of potential biomedical databases relevant to neurodegenerative diseases.62 +---- 88 88 89 - *Reference: [[List of PotentialDatabases>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/data/sources/list_of_potential_databases]]64 +=== Data Processing & Integration with Clinica.Run === 90 90 91 - ===**1.ster forAccess**===66 +Neurodiagnoses now supports **Clinica.Run**, an open-source neuroimaging platform designed for **multimodal data processing and reproducible neuroscience workflows**. 92 92 93 - Eachexternal database requires individual registration and access approval. Follow theofficial guidelinesof each database provider.68 +==== How It Works ==== 94 94 95 -* Ensure that you have completed all ethical approvals and data access agreements before integrating datasets into Neurodiagnoses. 96 -* Some repositories require a Data Usage Agreement (DUA) before downloading sensitive medical data. 97 97 98 -=== **2. Download & Prepare Data** === 71 +1. ((( 72 +**Neuroimaging Preprocessing:** 99 99 100 -Once access is granted, download datasets while complying with data usage policies. Ensure that the files meet Neurodiagnoses’ format requirements for smooth integration. 74 +* MRI, PET, EEG data is preprocessed using **Clinica.Run pipelines**. 75 +* Supports **longitudinal and cross-sectional analyses**. 76 +))) 77 +1. ((( 78 +**Automated Biomarker Extraction:** 101 101 102 -==== **Supported File Formats** ==== 80 +* Standardized extraction of **volumetric, metabolic, and functional biomarkers**. 81 +* Integration with machine learning models in Neurodiagnoses. 82 +))) 83 +1. ((( 84 +**Data Security & Compliance:** 103 103 104 -* Tabular Data: .csv, .tsv 105 -* Neuroimaging Data: .nii, .dcm 106 -* Genomic Data: .fasta, .vcf 107 -* Clinical Metadata: .json, .xml 86 +* Clinica.Run operates in **compliance with GDPR and HIPAA**. 87 +* Neuroimaging data remains **within the original storage environment**. 88 +))) 108 108 109 -==== **Mandatory Fields forIntegration**====90 +==== Implementation Steps ==== 110 110 111 -|=Field Name|=Description 112 -|Subject ID|Unique patient identifier 113 -|Diagnosis|Standardized disease classification 114 -|Biomarkers|CSF, plasma, or imaging biomarkers 115 -|Genetic Data|Whole-genome or exome sequencing 116 -|Neuroimaging Metadata|MRI/PET acquisition parameters 117 117 118 -=== **3. Upload Data to Neurodiagnoses** === 93 +1. Install **Clinica.Run** dependencies. 94 +1. Configure your **Clinica.Run pipeline** in clinica_run_config.json. 95 +1. Run the pipeline for **preprocessing and biomarker extraction**. 96 +1. Use processed neuroimaging data for **AI-driven diagnostics** in Neurodiagnoses. 119 119 120 - Oncepreprocessed,data canbeuploadedtoEBRAINSor GitHub.98 +For further information, refer to **[[Clinica.Run Documentation>>url:https://clinica.run/]]**. 121 121 122 -* ((( 123 -**Option 1: Upload to EBRAINS Bucket** 100 +==== ==== 124 124 125 -* Location: [[EBRAINS Neurodiagnoses Bucket>>url:https://wiki.ebrains.eu/bin/view/Collabs/neurodiagnoses/Bucket]] 126 -* Ensure correct metadata tagging before submission. 127 -))) 128 -* ((( 129 -**Option 2: Contribute via GitHub Repository** 102 +==== **Data Sources** ==== 130 130 131 -* Location: [[GitHub Data Repository>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/tree/main/data]] 132 -* Create a new folder under /data/ and include dataset description. 133 -))) 104 +[[List of potential sources of databases>>https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/data/sources/list_of_potential_databases]] 134 134 135 - //Note: For largedatasets, pleasecontact the projectadministratorsbefore uploading.//106 +**Biomedical Ontologies & Databases:** 136 136 137 -=== **4. Integrate Data into AI Models** === 108 +* **Human Phenotype Ontology (HPO)** for symptom annotation. 109 +* **Gene Ontology (GO)** for molecular and cellular processes. 138 138 139 - Onceuploaded, datasetsmustbe harmonizedandformatted beforeAI modeltraining.111 +**Dimensionality Reduction and Interpretability:** 140 140 141 -==== **Steps for Data Integration** ==== 113 +* **Evaluate interpretability** using metrics like the **Area Under the Interpretability Curve (AUIC)**. 114 +* **Leverage [[DEIBO>>https://github.com/Mellandd/DEIBO]] (Data-driven Embedding Interpretation Based on Ontologies)** to connect model dimensions to ontology concepts. 142 142 143 -* Open Jupyter Notebooks on EBRAINS to run preprocessing scripts. 144 -* Standardize neuroimaging and biomarker formats using harmonization tools. 145 -* Use machine learning models to handle missing data and feature extraction. 146 -* Train AI models with newly integrated patient cohorts. 147 -* Reference: [[Detailed instructions can be found in docs/data_processing.md>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/data_processing.md]]. 116 +**Neuroimaging & EEG/MEG Data:** 148 148 118 +* **MRI volumetric measures** for brain atrophy tracking. 119 +* **EEG functional connectivity patterns** (AI-Mind). 120 + 121 +**Clinical & Biomarker Data:** 122 + 123 +* **CSF biomarkers** (Amyloid-beta, Tau, Neurofilament Light). 124 +* **Sleep monitoring and actigraphy data** (ADIS). 125 + 126 +**Federated Learning Integration:** 127 + 128 +* **Secure multi-center data harmonization** (PROMINENT). 129 + 149 149 ---- 150 150 151 -== ** DatabaseSourcesTable** ==132 +==== **Annotation System for Multi-Modal Data** ==== 152 152 153 - ===**Where toInsertThis**===134 +To ensure **structured integration of diverse datasets**, **Neurodiagnoses** will implement an **AI-driven annotation system**, which will: 154 154 155 -* GitHub: [[docs/data_sources.md>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/data_sources.md]] 156 -* EBRAINS Wiki: Collabs/neurodiagnoses/Data Sources 136 +* **Assign standardized metadata tags** to diagnostic features. 137 +* **Provide contextual explanations** for AI-based classifications. 138 +* **Track temporal disease progression annotations** to identify long-term trends. 157 157 158 - === **Key Databases for Neurodiagnoses** ===140 +---- 159 159 160 -|=Database|=Focus Area|=Data Type|=Access Link 161 -|ADNI|Alzheimer's Disease|MRI, PET, CSF, cognitive tests|ADNI 162 -|PPMI|Parkinson’s Disease|Imaging, biospecimens|[[PPMI>>url:https://www.ppmi-info.org/]] 163 -|GP2|Genetic Data for PD|Whole-genome sequencing|[[GP2>>url:https://gp2.org/]] 164 -|Enroll-HD|Huntington’s Disease|Clinical, genetic, imaging|[[Enroll-HD>>url:https://enroll-hd.org/]] 165 -|GAAIN|Alzheimer's & Cognitive Decline|Multi-source data aggregation|[[GAAIN>>url:https://www.gaain.org/]] 166 -|UK Biobank|Population-wide studies|Genetic, imaging, health records|[[UK Biobank>>url:https://www.ukbiobank.ac.uk/]] 167 -|DPUK|Dementia & Aging|Imaging, genetics, lifestyle factors|[[DPUK>>url:https://www.dementiasplatform.uk/]] 168 -|PRION Registry|Prion Diseases|Clinical and genetic data|[[PRION Registry>>url:https://www.prionalliance.org/]] 169 -|DECIPHER|Rare Genetic Disorders|Genomic variants|DECIPHER 142 +== **2. AI-Based Analysis** == 170 170 171 - Ifyou knowarelevant dataset,submitaproposalin[[GitHubIssues>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/issues]].144 +==== **Machine Learning & Deep Learning Models** ==== 172 172 146 +**Risk Prediction Models:** 147 + 148 +* **LETHE’s cognitive risk prediction model** integrated into the annotation framework. 149 + 150 +**Biomarker Classification & Probabilistic Imputation:** 151 + 152 +* **KNN Imputer** and **Bayesian models** used for handling **missing biomarker data**. 153 + 154 +**Neuroimaging Feature Extraction:** 155 + 156 +* **MRI & EEG data** annotated with **neuroanatomical feature labels**. 157 + 158 +==== **AI-Powered Annotation System** ==== 159 + 160 +* Uses **SHAP-based interpretability tools** to explain model decisions. 161 +* Generates **automated clinical annotations** in structured reports. 162 +* Links findings to **standardized medical ontologies** (e.g., **SNOMED, HPO**). 163 + 173 173 ---- 174 174 175 -== ** Collaboration&Partnerships** ==166 +== **3. Diagnostic Framework & Clinical Decision Support** == 176 176 177 -=== ** WheretoInsertThis** ===168 +==== **Tridimensional Diagnostic Axes** ==== 178 178 179 -* GitHub: [[docs/collaboration.md>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/collaboration.md]] 180 -* EBRAINS Wiki: Collabs/neurodiagnoses/Collaborations 170 +**Axis 1: Etiology (Pathogenic Mechanisms)** 181 181 182 -=== **Partnering with Data Providers** === 172 +* Classification based on **genetic markers, cellular pathways, and environmental risk factors**. 173 +* **AI-assisted annotation** provides **causal interpretations** for clinical use. 183 183 184 - Beyond using existingdatasets,Neurodiagnosesseeks partnershipswithdata repositoriesto:175 +**Axis 2: Molecular Markers & Biomarkers** 185 185 186 -* Enable direct API-based data integration for real-time processing. 187 -* Co-develop harmonized AI-ready datasets with standardized annotations. 188 -* Secure funding opportunities through joint grant applications. 177 +* **Integration of CSF, blood, and neuroimaging biomarkers**. 178 +* **Structured annotation** highlights **biological pathways linked to diagnosis**. 189 189 190 - ===**InterestedinPartnering?**===180 +**Axis 3: Neuroanatomoclinical Correlations** 191 191 192 -If you represent a research consortium or database provider, reach out to explore data-sharing agreements. 182 +* **MRI and EEG data** provide anatomical and functional insights. 183 +* **AI-generated progression maps** annotate **brain structure-function relationships**. 193 193 194 - * Contact: [[info@neurodiagnoses.com>>mailto:info@neurodiagnoses.com]]185 +---- 195 195 187 +== **4. Computational Workflow & Annotation Pipelines** == 188 + 189 +==== **Data Processing Steps** ==== 190 + 191 +**Data Ingestion:** 192 + 193 +* **Harmonized datasets** stored in **EBRAINS Bucket**. 194 +* **Preprocessing pipelines** clean and standardize data. 195 + 196 +**Feature Engineering:** 197 + 198 +* **AI models** extract **clinically relevant patterns** from **EEG, MRI, and biomarkers**. 199 + 200 +**AI-Generated Annotations:** 201 + 202 +* **Automated tagging** of diagnostic features in **structured reports**. 203 +* **Explainability modules (SHAP, LIME)** ensure transparency in predictions. 204 + 205 +**Clinical Decision Support Integration:** 206 + 207 +* **AI-annotated findings** fed into **interactive dashboards**. 208 +* **Clinicians can adjust, validate, and modify annotations**. 209 + 196 196 ---- 197 197 198 -== ** FinalNotes** ==212 +== **5. Validation & Real-World Testing** == 199 199 200 - Neurodiagnoses continuously expands its dataecosystem to support AI-drivenclinicaldecision-making. Researchers and institutions are encouragedto contribute new datasets and methodologies.214 +==== **Prospective Clinical Study** ==== 201 201 202 -For additional technical documentation: 216 +* **Multi-center validation** of AI-based **annotations & risk stratifications**. 217 +* **Benchmarking against clinician-based diagnoses**. 218 +* **Real-world testing** of AI-powered **structured reporting**. 203 203 204 -* [[GitHub Repository>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses]] 205 -* [[EBRAINS Collaboration Page>>url:https://wiki.ebrains.eu/bin/view/Collabs/neurodiagnoses/]] 220 +==== **Quality Assurance & Explainability** ==== 206 206 207 -If you experience issues integrating data, open a [[GitHub Issue>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/issues]] or consult the EBRAINS Neurodiagnoses Forum. 222 +* **Annotations linked to structured knowledge graphs** for improved transparency. 223 +* **Interactive annotation editor** allows clinicians to validate AI outputs. 224 + 225 +---- 226 + 227 +== **6. Collaborative Development** == 228 + 229 +The project is **open to contributions** from **researchers, clinicians, and developers**. 230 + 231 +**Key tools include:** 232 + 233 +* **Jupyter Notebooks**: For data analysis and pipeline development. 234 +** Example: **probabilistic imputation** 235 +* **Wiki Pages**: For documenting methods and results. 236 +* **Drive and Bucket**: For sharing code, data, and outputs. 237 +* **Collaboration with related projects**: 238 +** Example: **Beyond the hype: AI in dementia – from early risk detection to disease treatment** 239 + 240 +---- 241 + 242 +== **7. Tools and Technologies** == 243 + 244 +==== **Programming Languages:** ==== 245 + 246 +* **Python** for AI and data processing. 247 + 248 +==== **Frameworks:** ==== 249 + 250 +* **TensorFlow** and **PyTorch** for machine learning. 251 +* **Flask** or **FastAPI** for backend services. 252 + 253 +==== **Visualization:** ==== 254 + 255 +* **Plotly** and **Matplotlib** for interactive and static visualizations. 256 + 257 +==== **EBRAINS Services:** ==== 258 + 259 +* **Collaboratory Lab** for running Notebooks. 260 +* **Buckets** for storing large datasets.