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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. It 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) **and** Disease Knowledge Transfer (DKT)**, which standardizes disease and biomarker classification across all CNS 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		-**Recommended Software**
	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		-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]].
	13	+----
10	10
11		-**Core Biomarker Categories**
	15	+== **Data Integration & External Databases** ==
12	12
13		-Within the Neurodiagnoses AI framework, biomarkers are categorized as follows:
	17	+=== **How to Use External Databases in Neurodiagnoses** ===
14	14
15		-|=**Category**|=**Description**
16		-|**Molecular Biomarkers**|Omics-based markers (genomic, transcriptomic, proteomic, metabolomic, lipidomic)
17		-|**Neuroimaging Biomarkers**|Structural (MRI, CT), Functional (fMRI, PET), Molecular Imaging (tau, amyloid, α-synuclein)
18		-|**Fluid Biomarkers**|CSF, plasma, blood-based markers for tau, amyloid, α-synuclein, TDP-43, GFAP, NfL, autoantiboides
19		-|**Neurophysiological Biomarkers**|EEG, MEG, evoked potentials (ERP), sleep-related markers
20		-|**Digital Biomarkers**|Gait analysis, cognitive/speech biomarkers, wearables data, EHR-based markers
21		-|**Clinical Phenotypic Markers**|Standardized clinical scores (MMSE, MoCA, CDR, UPDRS, ALSFRS, UHDRS)
22		-|**Genetic Biomarkers**|Risk alleles (APOE, LRRK2, MAPT, C9orf72, PRNP) and polygenic risk scores
23		-|**Environmental & Lifestyle Factors**|Toxins, infections, diet, microbiome, comorbidities
	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		-**Integrating External Databases into Neurodiagnoses**
	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		-To enhance diagnostic precision, Neurodiagnoses AI incorporates data from multiple biomedical and neurological research databases. Researchers can integrate external datasets by following these steps:
	24	+=== **Register for Access** ===
28	28
29		-1. (((
30		-**Register for Access**
	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		-* Each external database requires individual registration and access approval.
33		-* Ensure compliance with ethical approvals and data usage agreements before integrating datasets into Neurodiagnoses.
34		-* Some repositories may require a Data Usage Agreement (DUA) for sensitive medical data.
35		-)))
36		-1. (((
37		-**Download & Prepare Data**
	30	+=== **Download & Prepare Data** ===
38	38
39		-* Download datasets while adhering to database usage policies.
40		-* (((
41		-Ensure files meet Neurodiagnoses format requirements:
	32	+Once access is granted, download datasets **following compliance guidelines** and **format requirements** for integration.
42	42
43		-|=**Data Type**|=**Accepted Formats**
44		-|**Tabular Data**|.csv, .tsv
45		-|**Neuroimaging**|.nii, .dcm
46		-|**Genomic Data**|.fasta, .vcf
47		-|**Clinical Metadata**|.json, .xml
48		-)))
49		-* (((
50		-**Mandatory Fields for Integration**:
	34	+**Supported File Formats**
51	51
52		-* Subject ID: Unique patient identifier
53		-* Diagnosis: Standardized disease classification
54		-* Biomarkers: CSF, plasma, or imaging biomarkers
55		-* Genetic Data: Whole-genome or exome sequencing
56		-* Neuroimaging Metadata: MRI/PET acquisition parameters
57		-)))
58		-)))
59		-1. (((
60		-**Upload Data to Neurodiagnoses**
	36	+* **Tabular Data**: .csv, .tsv
	37	+* **Neuroimaging Data**: .nii, .dcm
	38	+* **Genomic Data**: .fasta, .vcf
	39	+* **Clinical Metadata**: .json, .xml
61	61
62		-* (((
63		-**Option 1: Upload to EBRAINS Bucket**
	41	+**Mandatory Fields for Integration**
64	64
65		-* Location: EBRAINS Neurodiagnoses Bucket
66		-* Ensure correct metadata tagging before submission.
67		-)))
68		-* (((
69		-**Option 2: Contribute via GitHub Repository**
	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
70	70
71		-* Location: GitHub Data Repository
72		-* Create a new folder under /data/ and include a dataset description.
73		-* For large datasets, contact project administrators before uploading.
74		-)))
75		-)))
76		-1. (((
77		-**Integrate Data into AI Models**
	50	+=== **Upload Data to Neurodiagnoses** ===
78	78
79		-* Open Jupyter Notebooks on EBRAINS to run preprocessing scripts.
80		-* Standardize neuroimaging and biomarker formats using harmonization tools.
81		-* Utilize machine learning models to handle missing data and feature extraction.
82		-* Train AI models with newly integrated patient cohorts.
	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]]
83	83
84		-**Reference**: See docs/data_processing.md for detailed instructions.
85		-)))
	55	+**For large datasets, please contact project administrators before uploading.**
86	86
87		-**AI-Driven Biomarker Categorization**
	57	+=== **Integrate Data into AI Models** ===
88	88
89		-Neurodiagnoses employs advanced AI models for biomarker classification:
	59	+Use **Jupyter Notebooks** on EBRAINS for **data preprocessing.**
	60	+Standardize data using **harmonization tools.**
	61	+Train AI models with **newly integrated datasets.**
90	90
91		-|=**Model Type**|=**Application**
92		-|**Graph Neural Networks (GNNs)**|Identify shared biomarker pathways across diseases
93		-|**Contrastive Learning**|Distinguish overlapping vs. unique biomarkers
94		-|**Multimodal Transformer Models**|Integrate imaging, omics, and clinical data
	63	+**Reference:** [[Data Processing Guide>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/data_processing.md]]
95	95
96		-**Collaboration & Partnerships**
	65	+----
97	97
98		-Neurodiagnoses actively seeks partnerships with data providers to:
	67	+== **AI-Powered Annotation & Machine Learning Models** ==
99	99
100		-* Enable API-based data integration for real-time processing.
101		-* Co-develop harmonized AI-ready datasets with standardized annotations.
102		-* Secure funding opportunities through joint grant applications.
	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		-**Interested in Partnering?**
	71	+=== **AI Model Categories** ===
105	105
106		-If you represent a research consortium or database provider, reach out to explore data-sharing agreements.
	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		-**Contact**: [[info@neurodiagnoses.com>>mailto:info@neurodiagnoses.com]]
	80	+**Reference:** [[AI Model Documentation>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/models.md]]
109	109
110		-**Final Notes**
	82	+----
111	111
112		-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.
	84	+== **Clinical Decision Support & Tridimensional Diagnostic Framework** ==
113	113
114		-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.
	86	+Neurodiagnoses generates **structured AI reports** for clinicians, combining:
115	115
116		-**For additional technical documentation and collaboration opportunities:**
	88	+**Probabilistic Diagnosis:** AI-generated ranking of potential diagnoses.
	89	+**Tridimensional Classification:** Standardized diagnostic reports based on:
117	117
118		-* **GitHub Repository:** [[Neurodiagnoses GitHub>>url:https://github.com/neurodiagnoses]]
119		-* **EBRAINS Collaboration Page:** [[EBRAINS Neurodiagnoses>>url:https://ebrains.eu/collabs/neurodiagnoses]]
	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.
120	120
121		-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.
	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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