Changes for page Methodology

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1 -== **Overview** ==
1 +Here is the updated **Methodology** section for the EBRAINS Wiki, incorporating the **Generalized Neuro Biomarker Ontology Categorization (Neuromarker)** for **biomarker classification across all neurodegenerative diseases**.
2 2  
3 -Neurodiagnoses develops a **tridimensional diagnostic framework** for **CNS diseases**, incorporating **AI-powered annotation tools** to improve **interpretability, standardization, and clinical utility.**
4 -
5 -This methodology integrates **multi-modal data**, including:
6 -**Genetic data** (whole-genome sequencing, polygenic risk scores).
7 -**Neuroimaging** (MRI, PET, EEG, MEG).
8 -**Neurophysiological data** (EEG-based biomarkers, sleep actigraphy).
9 -**CSF & Blood Biomarkers** (Amyloid-beta, Tau, Neurofilament Light).
10 -
11 -By applying **machine learning models**, Neurodiagnoses generates **structured, explainable diagnostic outputs** to assist **clinical decision-making** and **biomarker-driven patient stratification.**
12 -
13 13  ----
14 14  
15 -== **Data Integration & External Databases** ==
5 +== **Neurodiagnoses AI: Multimodal AI for Neurodiagnostic Predictions** ==
16 16  
17 -=== **How to Use External Databases in Neurodiagnoses** ===
7 +=== **Project Overview** ===
18 18  
19 -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.
9 +Neurodiagnoses AI implements **AI-driven diagnostic and prognostic models** for central nervous system (CNS) disorders, expanding 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**. This framework now incorporates **Neuromarker**, a **generalized biomarker ontology** that categorizes biomarkers across neurodegenerative diseases, enabling **standardized, cross-disease AI training**.
20 20  
21 -**Potential Data Sources**
22 -**Reference:** [[List of Potential Databases>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/data/sources/list_of_potential_databases]]
11 +== **Neuromarker: Generalized Biomarker Ontology** ==
23 23  
24 -=== **Register for Access** ===
13 +Neuromarker extends the **Common Alzheimer’s Disease Research Ontology (CADRO)** into a **cross-disease biomarker categorization framework** applicable to all neurodegenerative diseases (NDDs). It allows for **standardized classification, AI-based feature extraction, and multimodal integration**.
25 25  
26 -Each **external database** requires **individual registration** and approval.
27 -✔️ Follow the official **data access guidelines** of each provider.
28 -✔️ Ensure compliance with **ethical approvals** and **data-sharing agreements (DUAs).**
15 +=== **Core Biomarker Categories** ===
29 29  
30 -=== **Download & Prepare Data** ===
17 +The following ontology is used within **Neurodiagnoses AI** for biomarker categorization:
31 31  
32 -Once access is granted, download datasets **following compliance guidelines** and **format requirements** for integration.
19 +|=**Category**|=**Description**
20 +|**Molecular Biomarkers**|Omics-based markers (genomic, transcriptomic, proteomic, metabolomic, lipidomic)
21 +|**Neuroimaging Biomarkers**|Structural (MRI, CT), Functional (fMRI, PET), Molecular Imaging (tau, amyloid, α-synuclein)
22 +|**Fluid Biomarkers**|CSF, plasma, blood-based markers for tau, amyloid, α-synuclein, TDP-43, GFAP, NfL
23 +|**Neurophysiological Biomarkers**|EEG, MEG, evoked potentials (ERP), sleep-related markers
24 +|**Digital Biomarkers**|Gait analysis, cognitive/speech biomarkers, wearables data, EHR-based markers
25 +|**Clinical Phenotypic Markers**|Standardized clinical scores (MMSE, MoCA, CDR, UPDRS, ALSFRS, UHDRS)
26 +|**Genetic Biomarkers**|Risk alleles (APOE, LRRK2, MAPT, C9orf72, PRNP) and polygenic risk scores
27 +|**Environmental & Lifestyle Factors**|Toxins, infections, diet, microbiome, comorbidities
33 33  
34 -**Supported File Formats**
29 +----
35 35  
36 -* **Tabular Data**: .csv, .tsv
37 -* **Neuroimaging Data**: .nii, .dcm
38 -* **Genomic Data**: .fasta, .vcf
39 -* **Clinical Metadata**: .json, .xml
31 +== **How to Use External Databases in Neurodiagnoses** ==
40 40  
41 -**Mandatory Fields for Integration**
33 +To enhance diagnostic accuracy, Neurodiagnoses AI integrates data from **multiple biomedical and neurological research databases**. Researchers can follow these steps to access, prepare, and integrate data into the Neurodiagnoses framework.
42 42  
43 -|=**Field Name**|=**Description**
44 -|**Subject ID**|Unique patient identifier
45 -|**Diagnosis**|Standardized disease classification
46 -|**Biomarkers**|CSF, plasma, or imaging biomarkers
47 -|**Genetic Data**|Whole-genome or exome sequencing
48 -|**Neuroimaging Metadata**|MRI/PET acquisition parameters
35 +=== **Potential Data Sources** ===
49 49  
50 -=== **Upload Data to Neurodiagnoses** ===
37 +Neurodiagnoses maintains an **updated list** of biomedical datasets relevant to neurodegenerative diseases:
51 51  
52 -**Option 1:** Upload to **EBRAINS Bucket** → [[Neurodiagnoses Data Storage>>url:https://wiki.ebrains.eu/bin/view/Collabs/neurodiagnoses/Bucket]]
53 -**Option 2:** Contribute via **GitHub Repository** → [[GitHub Data Repository>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/tree/main/data]]
39 +* **ADNI**: Alzheimer's Disease Imaging & Biomarkers → [[ADNI>>url:https://adni.loni.usc.edu/]]
40 +* **PPMI**: Parkinson’s Disease Imaging & Biospecimens → [[PPMI>>url:https://www.ppmi-info.org/]]
41 +* **GP2**: Whole-Genome Sequencing for PD → [[GP2>>url:https://gp2.org/]]
42 +* **Enroll-HD**: Huntington’s Disease Clinical & Genetic Data → [[Enroll-HD>>url:https://www.enroll-hd.org/]]
43 +* **GAAIN**: Multi-Source Alzheimer’s Data Aggregation → [[GAAIN>>url:https://gaain.org/]]
44 +* **UK Biobank**: Population-Wide Genetic, Imaging & Health Records → [[UK Biobank>>url:https://www.ukbiobank.ac.uk/]]
45 +* **DPUK**: Dementia & Aging Data → [[DPUK>>url:https://www.dementiasplatform.uk/]]
46 +* **PRION Registry**: Prion Diseases Clinical & Genetic Data → [[PRION Registry>>url:https://prionregistry.org/]]
47 +* **DECIPHER**: Rare Genetic Disorder Genomic Variants → [[DECIPHER>>url:https://decipher.sanger.ac.uk/]]
54 54  
55 -**For large datasets, please contact project administrators before uploading.**
49 +----
56 56  
57 -=== **Integrate Data into AI Models** ===
51 +== **1. Register for Access** ==
58 58  
59 -Use **Jupyter Notebooks** on EBRAINS for **data preprocessing.**
60 -Standardize data using **harmonization tools.**
61 -Train AI models with **newly integrated datasets.**
53 +* Each external database requires **individual registration and access approval**.
54 +* Ensure compliance with **ethical approvals and data usage agreements** before integrating datasets into Neurodiagnoses.
55 +* Some repositories may require a **Data Usage Agreement (DUA)** for sensitive medical data.
62 62  
63 -**Reference:** [[Data Processing Guide>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/data_processing.md]]
64 -
65 65  ----
66 66  
67 -== **AI-Powered Annotation & Machine Learning Models** ==
59 +== **2. Download & Prepare Data** ==
68 68  
69 -Neurodiagnoses applies **advanced machine learning models** to classify CNS diseases, extract features from **biomarkers and neuroimaging**, and provide **AI-powered annotation.**
61 +* Download datasets while adhering to **database usage policies**.
62 +* Ensure files meet **Neurodiagnoses format requirements**:
70 70  
71 -=== **AI Model Categories** ===
64 +|=**Data Type**|=**Accepted Formats**
65 +|**Tabular Data**|.csv, .tsv
66 +|**Neuroimaging**|.nii, .dcm
67 +|**Genomic Data**|.fasta, .vcf
68 +|**Clinical Metadata**|.json, .xml
72 72  
73 -|=**Model Type**|=**Function**|=**Example Algorithms**
74 -|**Probabilistic Diagnosis**|Assigns probability scores to multiple CNS disorders.|Random Forest, XGBoost, Bayesian Networks
75 -|**Tridimensional Diagnosis**|Classifies disorders based on Etiology, Biomarkers, and Neuroanatomical Correlations.|CNNs, Transformers, Autoencoders
76 -|**Biomarker Prediction**|Predicts missing biomarker values using regression.|KNN Imputation, Bayesian Estimation
77 -|**Neuroimaging Feature Extraction**|Extracts patterns from MRI, PET, EEG.|CNNs, Graph Neural Networks
78 -|**Clinical Decision Support**|Generates AI-driven diagnostic reports.|SHAP Explainability Tools
70 +* **Mandatory Fields for Integration**:
71 +** **Subject ID**: Unique patient identifier
72 +** **Diagnosis**: Standardized disease classification
73 +** **Biomarkers**: CSF, plasma, or imaging biomarkers
74 +** **Genetic Data**: Whole-genome or exome sequencing
75 +** **Neuroimaging Metadata**: MRI/PET acquisition parameters
79 79  
80 -**Reference:** [[AI Model Documentation>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/models.md]]
81 -
82 82  ----
83 83  
84 -== **Clinical Decision Support & Tridimensional Diagnostic Framework** ==
79 +== **3. Upload Data to Neurodiagnoses** ==
85 85  
86 -Neurodiagnoses generates **structured AI reports** for clinicians, combining:
81 +=== **Option 1: Upload to EBRAINS Bucket** ===
87 87  
88 -**Probabilistic Diagnosis:** AI-generated ranking of potential diagnoses.
89 -**Tridimensional Classification:** Standardized diagnostic reports based on:
83 +* Location: **EBRAINS Neurodiagnoses Bucket**
84 +* Ensure **correct metadata tagging** before submission.
90 90  
91 -1. **Axis 1:** **Etiology** → Genetic, Autoimmune, Prion, Toxic, Vascular.
92 -1. **Axis 2:** **Molecular Markers** → CSF, Neuroinflammation, EEG biomarkers.
93 -1. **Axis 3:** **Neuroanatomoclinical Correlations** → MRI atrophy, PET.
86 +=== **Option 2: Contribute via GitHub Repository** ===
94 94  
95 -**Reference:** [[Tridimensional Classification Guide>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/classification.md]]
88 +* Location: **GitHub Data Repository**
89 +* Create a **new folder under /data/** and include a **dataset description**.
90 +* **For large datasets**, contact project administrators before uploading.
96 96  
97 97  ----
98 98  
99 -== **Data Security, Compliance & Federated Learning** ==
94 +== **4. Integrate Data into AI Models** ==
100 100  
101 -✔ **Privacy-Preserving AI**: Implements **Federated Learning**, ensuring that patient data **never leaves** local institutions.
102 -✔ **Secure Data Access**: Data remains **stored in EBRAINS MIP servers** using **differential privacy techniques.**
103 -✔ **Ethical & GDPR Compliance**: Data-sharing agreements **must be signed** before use.
96 +* Open **Jupyter Notebooks** on EBRAINS to run **preprocessing scripts**.
97 +* **Standardize neuroimaging and biomarker formats** using harmonization tools.
98 +* Use **machine learning models** to handle **missing data** and **feature extraction**.
99 +* Train AI models with **newly integrated patient cohorts**.
104 104  
105 -**Reference:** [[Data Protection & Federated Learning>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/security.md]]
101 +**Reference**: See docs/data_processing.md for detailed instructions.
106 106  
107 107  ----
108 108  
109 -== **Data Processing & Integration with Clinica.Run** ==
105 +== **AI-Driven Biomarker Categorization** ==
110 110  
111 -Neurodiagnoses now supports **Clinica.Run**, an **open-source neuroimaging platform** for **multimodal data processing.**
107 +Neurodiagnoses employs **AI models** for biomarker classification:
112 112  
113 -=== **How It Works** ===
109 +|=**Model Type**|=**Application**
110 +|**Graph Neural Networks (GNNs)**|Identify shared biomarker pathways across diseases
111 +|**Contrastive Learning**|Distinguish overlapping vs. unique biomarkers
112 +|**Multimodal Transformer Models**|Integrate imaging, omics, and clinical data
114 114  
115 -✔ **Neuroimaging Preprocessing**: MRI, PET, EEG data is preprocessed using **Clinica.Run pipelines.**
116 -✔ **Automated Biomarker Extraction**: Extracts volumetric, metabolic, and functional biomarkers.
117 -✔ **Data Security & Compliance**: Clinica.Run is **GDPR & HIPAA-compliant.**
114 +----
118 118  
119 -=== **Implementation Steps** ===
116 +== [[image:workflow neurodiagnoses.png]] ==
120 120  
121 -1. Install **Clinica.Run** dependencies.
122 -1. Configure **Clinica.Run pipeline** in clinica_run_config.json.
123 -1. Run **biomarker extraction pipelines** for AI-based diagnostics.
118 +== **Collaboration & Partnerships** ==
124 124  
125 -**Reference:** [[Clinica.Run Documentation>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/clinica_run.md]]
120 +=== **Partnering with Data Providers** ===
126 126  
127 -----
122 +Neurodiagnoses seeks partnerships with data repositories to:
128 128  
129 -== **Collaborative Development & Research** ==
124 +* Enable **API-based data integration** for real-time processing.
125 +* Co-develop **harmonized AI-ready datasets** with standardized annotations.
126 +* Secure **funding opportunities** through joint grant applications.
130 130  
131 -**We Use GitHub to Develop AI Models & Store Research Data**
128 +**Interested in Partnering?**
132 132  
133 -* **GitHub Repository:** AI model training scripts.
134 -* **GitHub Issues:** Tracks ongoing research questions.
135 -* **GitHub Wiki:** Project documentation & user guides.
130 +* If you represent a **research consortium or database provider**, reach out to explore **data-sharing agreements**.
131 +* **Contact**: [[info@neurodiagnoses.com>>mailto:info@neurodiagnoses.com]]
136 136  
137 -**We Use EBRAINS for Data & Collaboration**
133 +----
138 138  
139 -* **EBRAINS Buckets:** Large-scale neuroimaging and biomarker storage.
140 -* **EBRAINS Jupyter Notebooks:** Cloud-based AI model execution.
141 -* **EBRAINS Wiki:** Research documentation and updates.
135 +== **Final Notes** ==
142 142  
143 -**Join the Project Forum:** [[GitHub Discussions>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/discussions]]
137 +Neurodiagnoses continuously expands its **data ecosystem** to support **AI-driven clinical decision-making**. Researchers and institutions are encouraged to **contribute new datasets and methodologies**.
144 144  
145 -----
139 +**For additional technical documentation**:
146 146  
147 -**For Additional Documentation:**
141 +* **GitHub Repository**: [[Neurodiagnoses GitHub>>url:https://github.com/neurodiagnoses]]
142 +* **EBRAINS Collaboration Page**: [[EBRAINS Neurodiagnoses>>url:https://ebrains.eu/collabs/neurodiagnoses]]
148 148  
149 -* **GitHub Repository:** [[Neurodiagnoses AI Models>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses]]
150 -* **EBRAINS Wiki:** [[Neurodiagnoses Research Collaboration>>url:https://wiki.ebrains.eu/bin/view/Collabs/neurodiagnoses/]]
144 +**If you experience issues integrating data**, open a **GitHub Issue** or consult the **EBRAINS Neurodiagnoses Forum**.
151 151  
152 152  ----
153 153  
154 -**Neurodiagnoses is Open for Contributions Join Us Today!**
148 +This **updated methodology** now incorporates [[https:~~/~~/github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/data/biomarker_ontology>>https://Neuromarker]] for standardized biomarker classification, enabling **cross-disease AI training** across neurodegenerative disorders.
workflow neurodiagnoses.png
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