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1		-==== **Overview** ====
	1	+== **Overview** ==
2	2
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**.
	3	+Neurodiagnoses develops a **tridimensional diagnostic framework** for **CNS diseases**, incorporating **AI-powered annotation tools** to improve **interpretability, standardization, and clinical utility.**
4	4
5		-=== **Workflow** ===
	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).
6	6
7		-1. (((
8		-**We Use [[https:~~/~~/github.com/users/manuelmenendezgonzalez/projects/1>>https://GitHub for AI Development]]**
	11	+By applying **machine learning models**, Neurodiagnoses generates **structured, explainable diagnostic outputs** to assist **clinical decision-making** and **biomarker-driven patient stratification.**
9	9
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**
	13	+----
15	15
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		-)))
	15	+== **Data Integration & External Databases** ==
20	20
21		-----
	17	+=== **How to Use External Databases in Neurodiagnoses** ===
22	22
23		-=== **1. Data Integration** ===
	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.
24	24
25		-==== **Data Sources** ====
	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]]
26	26
27		-**Biomedical Ontologies & Databases:**
	24	+=== **Register for Access** ===
28	28
29		-* **Human Phenotype Ontology (HPO)** for symptom annotation.
30		-* **Gene Ontology (GO)** for molecular and cellular processes.
	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).**
31	31
32		-**Dimensionality Reduction and Interpretability:**
	30	+=== **Download & Prepare Data** ===
33	33
34		-* **Evaluate interpretability** using metrics like the **Area Under the Interpretability Curve (AUIC)**.
35		-* **Leverage DEIBO (Data-driven Embedding Interpretation Based on Ontologies)** to connect model dimensions to ontology concepts.
	32	+Once access is granted, download datasets **following compliance guidelines** and **format requirements** for integration.
36	36
37		-**Neuroimaging & EEG/MEG Data:**
	34	+**Supported File Formats**
38	38
39		-* **MRI volumetric measures** for brain atrophy tracking.
40		-* **EEG functional connectivity patterns** (AI-Mind).
	36	+* **Tabular Data**: .csv, .tsv
	37	+* **Neuroimaging Data**: .nii, .dcm
	38	+* **Genomic Data**: .fasta, .vcf
	39	+* **Clinical Metadata**: .json, .xml
41	41
42		-**Clinical & Biomarker Data:**
	41	+**Mandatory Fields for Integration**
43	43
44		-* **CSF biomarkers** (Amyloid-beta, Tau, Neurofilament Light).
45		-* **Sleep monitoring and actigraphy data** (ADIS).
	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
46	46
47		-**Federated Learning Integration:**
	50	+=== **Upload Data to Neurodiagnoses** ===
48	48
49		-* **Secure multi-center data harmonization** (PROMINENT).
	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]]
50	50
51		-----
	55	+**For large datasets, please contact project administrators before uploading.**
52	52
53		-==== **Annotation System for Multi-Modal Data** ====
	57	+=== **Integrate Data into AI Models** ===
54	54
55		-To ensure **structured integration of diverse datasets**, **Neurodiagnoses** will implement an **AI-driven annotation system**, which will:
	59	+Use **Jupyter Notebooks** on EBRAINS for **data preprocessing.**
	60	+Standardize data using **harmonization tools.**
	61	+Train AI models with **newly integrated datasets.**
56	56
57		-* **Assign standardized metadata tags** to diagnostic features.
58		-* **Provide contextual explanations** for AI-based classifications.
59		-* **Track temporal disease progression annotations** to identify long-term trends.
	63	+**Reference:** [[Data Processing Guide>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/data_processing.md]]
60	60
61	61	----
62	62
63		-=== **2. AI-Based Analysis** ===
	67	+== **AI-Powered Annotation & Machine Learning Models** ==
64	64
65		-==== **Machine Learning & Deep Learning Models** ====
	69	+Neurodiagnoses applies **advanced machine learning models** to classify CNS diseases, extract features from **biomarkers and neuroimaging**, and provide **AI-powered annotation.**
66	66
67		-**Risk Prediction Models:**
	71	+=== **AI Model Categories** ===
68	68
69		-* **LETHE’s cognitive risk prediction model** integrated into the annotation framework.
	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	70
71		-**Biomarker Classification & Probabilistic Imputation:**
	80	+**Reference:** [[AI Model Documentation>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/models.md]]
72	72
73		-* **KNN Imputer** and **Bayesian models** used for handling **missing biomarker data**.
74		-
75		-**Neuroimaging Feature Extraction:**
76		-
77		-* **MRI & EEG data** annotated with **neuroanatomical feature labels**.
78		-
79		-==== **AI-Powered Annotation System** ====
80		-
81		-* Uses **SHAP-based interpretability tools** to explain model decisions.
82		-* Generates **automated clinical annotations** in structured reports.
83		-* Links findings to **standardized medical ontologies** (e.g., **SNOMED, HPO**).
84		-
85	85	----
86	86
87		-=== **3. Diagnostic Framework & Clinical Decision Support** ===
	84	+== **Clinical Decision Support & Tridimensional Diagnostic Framework** ==
88	88
89		-==== **Tridimensional Diagnostic Axes** ====
	86	+Neurodiagnoses generates **structured AI reports** for clinicians, combining:
90	90
91		-**Axis 1: Etiology (Pathogenic Mechanisms)**
	88	+**Probabilistic Diagnosis:** AI-generated ranking of potential diagnoses.
	89	+**Tridimensional Classification:** Standardized diagnostic reports based on:
92	92
93		-* Classification based on **genetic markers, cellular pathways, and environmental risk factors**.
94		-* **AI-assisted annotation** provides **causal interpretations** for clinical use.
	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.
95	95
96		-**Axis 2: Molecular Markers & Biomarkers**
	95	+**Reference:** [[Tridimensional Classification Guide>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/classification.md]]
97	97
98		-* **Integration of CSF, blood, and neuroimaging biomarkers**.
99		-* **Structured annotation** highlights **biological pathways linked to diagnosis**.
100		-
101		-**Axis 3: Neuroanatomoclinical Correlations**
102		-
103		-* **MRI and EEG data** provide anatomical and functional insights.
104		-* **AI-generated progression maps** annotate **brain structure-function relationships**.
105		-
106	106	----
107	107
108		-=== **4. Computational Workflow & Annotation Pipelines** ===
	99	+== **Data Security, Compliance & Federated Learning** ==
109	109
110		-==== **Data Processing Steps** ====
	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.
111	111
112		-**Data Ingestion:**
	105	+**Reference:** [[Data Protection & Federated Learning>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/security.md]]
113	113
114		-* **Harmonized datasets** stored in **EBRAINS Bucket**.
115		-* **Preprocessing pipelines** clean and standardize data.
116		-
117		-**Feature Engineering:**
118		-
119		-* **AI models** extract **clinically relevant patterns** from **EEG, MRI, and biomarkers**.
120		-
121		-**AI-Generated Annotations:**
122		-
123		-* **Automated tagging** of diagnostic features in **structured reports**.
124		-* **Explainability modules (SHAP, LIME)** ensure transparency in predictions.
125		-
126		-**Clinical Decision Support Integration:**
127		-
128		-* **AI-annotated findings** fed into **interactive dashboards**.
129		-* **Clinicians can adjust, validate, and modify annotations**.
130		-
131	131	----
132	132
133		-=== **5. Validation & Real-World Testing** ===
	109	+== **Data Processing & Integration with Clinica.Run** ==
134	134
135		-==== **Prospective Clinical Study** ====
	111	+Neurodiagnoses now supports **Clinica.Run**, an **open-source neuroimaging platform** for **multimodal data processing.**
136	136
137		-* **Multi-center validation** of AI-based **annotations & risk stratifications**.
138		-* **Benchmarking against clinician-based diagnoses**.
139		-* **Real-world testing** of AI-powered **structured reporting**.
	113	+=== **How It Works** ===
140	140
141		-==== **Quality Assurance & Explainability** ====
	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.**
142	142
143		-* **Annotations linked to structured knowledge graphs** for improved transparency.
144		-* **Interactive annotation editor** allows clinicians to validate AI outputs.
	119	+=== **Implementation Steps** ===
145	145
146		-----
	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.
147	147
148		-=== **6. Collaborative Development** ===
	125	+**Reference:** [[Clinica.Run Documentation>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/clinica_run.md]]
149	149
150		-The project is **open to contributions** from **researchers, clinicians, and developers**.
151		-
152		-**Key tools include:**
153		-
154		-* **Jupyter Notebooks**: For data analysis and pipeline development.
155		-** Example: **probabilistic imputation**
156		-* **Wiki Pages**: For documenting methods and results.
157		-* **Drive and Bucket**: For sharing code, data, and outputs.
158		-* **Collaboration with related projects**:
159		-** Example: **Beyond the hype: AI in dementia – from early risk detection to disease treatment**
160		-
161	161	----
162	162
163		-=== **7. Tools and Technologies** ===
	129	+== **Collaborative Development & Research** ==
164	164
165		-==== **Programming Languages:** ====
	131	+**We Use GitHub to Develop AI Models & Store Research Data**
166	166
167		-* **Python** for AI and data processing.
	133	+* **GitHub Repository:** AI model training scripts.
	134	+* **GitHub Issues:** Tracks ongoing research questions.
	135	+* **GitHub Wiki:** Project documentation & user guides.
168	168
169		-==== **Frameworks:** ====
	137	+**We Use EBRAINS for Data & Collaboration**
170	170
171		-* **TensorFlow** and **PyTorch** for machine learning.
172		-* **Flask** or **FastAPI** for backend services.
	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.
173	173
174		-==== **Visualization:** ====
	143	+**Join the Project Forum:** [[GitHub Discussions>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/discussions]]
175	175
176		-* **Plotly** and **Matplotlib** for interactive and static visualizations.
	145	+----
177	177
178		-==== **EBRAINS Services:** ====
	147	+**For Additional Documentation:**
179	179
180		-* **Collaboratory Lab** for running Notebooks.
181		-* **Buckets** for storing large datasets.
	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/]]
182	182
183	183	----
184	184
185		-=== **Why This Matters** ===
186		-
187		-* **The annotation system ensures that AI-generated insights are structured, interpretable, and clinically meaningful.**
188		-* **It enables real-time tracking of disease progression across the three diagnostic axes.**
189		-* **It facilitates integration with electronic health records and decision-support tools, improving AI adoption in clinical workflows.**
	154	+**Neurodiagnoses is Open for Contributions – Join Us Today!**