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1		-**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.
	1	+== **Overview** ==
2	2
3		-**Neuromarker: Generalized Biomarker Ontology**
	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		-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.
	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		-**Core Biomarker Categories**
	11	+By applying **machine learning models**, Neurodiagnoses generates **structured, explainable diagnostic outputs** to assist **clinical decision-making** and **biomarker-driven patient stratification.**
8	8
9		-Within the Neurodiagnoses AI framework, biomarkers are categorized as follows:
	13	+----
10	10
11		-|=**Category**|=**Description**
12		-|**Molecular Biomarkers**|Omics-based markers (genomic, transcriptomic, proteomic, metabolomic, lipidomic)
13		-|**Neuroimaging Biomarkers**|Structural (MRI, CT), Functional (fMRI, PET), Molecular Imaging (tau, amyloid, α-synuclein)
14		-|**Fluid Biomarkers**|CSF, plasma, blood-based markers for tau, amyloid, α-synuclein, TDP-43, GFAP, NfL, autoantiboides
15		-|**Neurophysiological Biomarkers**|EEG, MEG, evoked potentials (ERP), sleep-related markers
16		-|**Digital Biomarkers**|Gait analysis, cognitive/speech biomarkers, wearables data, EHR-based markers
17		-|**Clinical Phenotypic Markers**|Standardized clinical scores (MMSE, MoCA, CDR, UPDRS, ALSFRS, UHDRS)
18		-|**Genetic Biomarkers**|Risk alleles (APOE, LRRK2, MAPT, C9orf72, PRNP) and polygenic risk scores
19		-|**Environmental & Lifestyle Factors**|Toxins, infections, diet, microbiome, comorbidities
	15	+== **Data Integration & External Databases** ==
20	20
21		-**Integrating External Databases into Neurodiagnoses**
	17	+=== **How to Use External Databases in Neurodiagnoses** ===
22	22
23		-To enhance diagnostic precision, Neurodiagnoses AI incorporates data from multiple biomedical and neurological research databases. Researchers can integrate external datasets by following these steps:
	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		-1. (((
26		-**Register for Access**
	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]]
27	27
28		-* Each external database requires individual registration and access approval.
29		-* Ensure compliance with ethical approvals and data usage agreements before integrating datasets into Neurodiagnoses.
30		-* Some repositories may require a Data Usage Agreement (DUA) for sensitive medical data.
31		-)))
32		-1. (((
33		-**Download & Prepare Data**
	24	+=== **Register for Access** ===
34	34
35		-* Download datasets while adhering to database usage policies.
36		-* (((
37		-Ensure files meet Neurodiagnoses format requirements:
	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).**
38	38
39		-|=**Data Type**|=**Accepted Formats**
40		-|**Tabular Data**|.csv, .tsv
41		-|**Neuroimaging**|.nii, .dcm
42		-|**Genomic Data**|.fasta, .vcf
43		-|**Clinical Metadata**|.json, .xml
44		-)))
45		-* (((
46		-**Mandatory Fields for Integration**:
	30	+=== **Download & Prepare Data** ===
47	47
48		-* Subject ID: Unique patient identifier
49		-* Diagnosis: Standardized disease classification
50		-* Biomarkers: CSF, plasma, or imaging biomarkers
51		-* Genetic Data: Whole-genome or exome sequencing
52		-* Neuroimaging Metadata: MRI/PET acquisition parameters
53		-)))
54		-)))
55		-1. (((
56		-**Upload Data to Neurodiagnoses**
	32	+Once access is granted, download datasets **following compliance guidelines** and **format requirements** for integration.
57	57
58		-* (((
59		-**Option 1: Upload to EBRAINS Bucket**
	34	+**Supported File Formats**
60	60
61		-* Location: EBRAINS Neurodiagnoses Bucket
62		-* Ensure correct metadata tagging before submission.
63		-)))
64		-* (((
65		-**Option 2: Contribute via GitHub Repository**
	36	+* **Tabular Data**: .csv, .tsv
	37	+* **Neuroimaging Data**: .nii, .dcm
	38	+* **Genomic Data**: .fasta, .vcf
	39	+* **Clinical Metadata**: .json, .xml
66	66
67		-* Location: GitHub Data Repository
68		-* Create a new folder under /data/ and include a dataset description.
69		-* For large datasets, contact project administrators before uploading.
70		-)))
71		-)))
72		-1. (((
73		-**Integrate Data into AI Models**
	41	+**Mandatory Fields for Integration**
74	74
75		-* Open Jupyter Notebooks on EBRAINS to run preprocessing scripts.
76		-* Standardize neuroimaging and biomarker formats using harmonization tools.
77		-* Utilize machine learning models to handle missing data and feature extraction.
78		-* Train AI models with newly integrated patient cohorts.
	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
79	79
80		-**Reference**: See docs/data_processing.md for detailed instructions.
81		-)))
	50	+=== **Upload Data to Neurodiagnoses** ===
82	82
83		-**AI-Driven Biomarker Categorization**
	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]]
84	84
85		-Neurodiagnoses employs advanced AI models for biomarker classification:
	55	+**For large datasets, please contact project administrators before uploading.**
86	86
87		-|=**Model Type**|=**Application**
88		-|**Graph Neural Networks (GNNs)**|Identify shared biomarker pathways across diseases
89		-|**Contrastive Learning**|Distinguish overlapping vs. unique biomarkers
90		-|**Multimodal Transformer Models**|Integrate imaging, omics, and clinical data
	57	+=== **Integrate Data into AI Models** ===
91	91
92		-**Collaboration & Partnerships**
	59	+Use **Jupyter Notebooks** on EBRAINS for **data preprocessing.**
	60	+Standardize data using **harmonization tools.**
	61	+Train AI models with **newly integrated datasets.**
93	93
94		-Neurodiagnoses actively seeks partnerships with data providers to:
	63	+**Reference:** [[Data Processing Guide>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/data_processing.md]]
95	95
96		-* Enable API-based data integration for real-time processing.
97		-* Co-develop harmonized AI-ready datasets with standardized annotations.
98		-* Secure funding opportunities through joint grant applications.
	65	+----
99	99
100		-**Interested in Partnering?**
	67	+== **AI-Powered Annotation & Machine Learning Models** ==
101	101
102		-If you represent a research consortium or database provider, reach out to explore data-sharing agreements.
	69	+Neurodiagnoses applies **advanced machine learning models** to classify CNS diseases, extract features from **biomarkers and neuroimaging**, and provide **AI-powered annotation.**
103	103
104		-**Contact**: [[info@neurodiagnoses.com>>mailto:info@neurodiagnoses.com]]
	71	+=== **AI Model Categories** ===
105	105
106		-**Final Notes**
	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
107	107
108		-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.
	80	+**Reference:** [[AI Model Documentation>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/models.md]]
109	109
110		-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.
	82	+----
111	111
112		-**For additional technical documentation and collaboration opportunities:**
	84	+== **Clinical Decision Support & Tridimensional Diagnostic Framework** ==
113	113
114		-* **GitHub Repository:** [[Neurodiagnoses GitHub>>url:https://github.com/neurodiagnoses]]
115		-* **EBRAINS Collaboration Page:** [[EBRAINS Neurodiagnoses>>url:https://ebrains.eu/collabs/neurodiagnoses]]
	86	+Neurodiagnoses generates **structured AI reports** for clinicians, combining:
116	116
117		-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.
	88	+**Probabilistic Diagnosis:** AI-generated ranking of potential diagnoses.
	89	+**Tridimensional Classification:** Standardized diagnostic reports based on:
	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.
	94	+
	95	+**Reference:** [[Tridimensional Classification Guide>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/classification.md]]
	96	+
	97	+----
	98	+
	99	+== **Data Security, Compliance & Federated Learning** ==
	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.
	104	+
	105	+**Reference:** [[Data Protection & Federated Learning>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/security.md]]
	106	+
	107	+----
	108	+
	109	+== **Data Processing & Integration with Clinica.Run** ==
	110	+
	111	+Neurodiagnoses now supports **Clinica.Run**, an **open-source neuroimaging platform** for **multimodal data processing.**
	112	+
	113	+=== **How It Works** ===
	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.**
	118	+
	119	+=== **Implementation Steps** ===
	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.
	124	+
	125	+**Reference:** [[Clinica.Run Documentation>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/clinica_run.md]]
	126	+
	127	+----
	128	+
	129	+== **Collaborative Development & Research** ==
	130	+
	131	+**We Use GitHub to Develop AI Models & Store Research Data**
	132	+
	133	+* **GitHub Repository:** AI model training scripts.
	134	+* **GitHub Issues:** Tracks ongoing research questions.
	135	+* **GitHub Wiki:** Project documentation & user guides.
	136	+
	137	+**We Use EBRAINS for Data & Collaboration**
	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.
	142	+
	143	+**Join the Project Forum:** [[GitHub Discussions>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/discussions]]
	144	+
	145	+----
	146	+
	147	+**For Additional Documentation:**
	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/]]
	151	+
	152	+----
	153	+
	154	+**Neurodiagnoses is Open for Contributions – Join Us Today!**

workflow neurodiagnoses.png

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