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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. The methodology integrates multi-modal data, including genetic, neuroimaging, neurophysiological, and biomarker datasets, and applies machine learning models to generate structured, explainable diagnostic outputs.
4		-
5	5	----
6	6
7		-== **How to Use External Databases in Neurodiagnoses** ==
	5	+== **Neurodiagnoses AI: Multimodal AI for Neurodiagnostic Predictions** ==
8	8
9		-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.
	7	+=== **Project Overview** ===
10	10
11		-=== **Potential Data Sources** ===
	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**.
12	12
13		-Neurodiagnoses maintains an updated list of potential biomedical databases relevant to neurodegenerative diseases.
	11	+== **Neuromarker: Generalized Biomarker Ontology** ==
14	14
15		-* Reference: [[List of Potential Databases>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/data/sources/list_of_potential_databases]]
	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**.
16	16
17		-=== **1. Register for Access** ===
	15	+=== **Core Biomarker Categories** ===
18	18
19		-Each external database requires individual registration and access approval. Follow the official guidelines of each database provider.
	17	+The following ontology is used within **Neurodiagnoses AI** for biomarker categorization:
20	20
21		-* Ensure that you have completed all ethical approvals and data access agreements before integrating datasets into Neurodiagnoses.
22		-* Some repositories require a Data Usage Agreement (DUA) before downloading sensitive medical data.
	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
23	23
24		-=== **2. Download & Prepare Data** ===
	29	+----
25	25
26		-Once access is granted, download datasets while complying with data usage policies. Ensure that the files meet Neurodiagnoses’ format requirements for smooth integration.
	31	+== **How to Use External Databases in Neurodiagnoses** ==
27	27
28		-==== **Supported File Formats** ====
	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.
29	29
30		-* Tabular Data: .csv, .tsv
31		-* Neuroimaging Data: .nii, .dcm
32		-* Genomic Data: .fasta, .vcf
33		-* Clinical Metadata: .json, .xml
	35	+=== **Potential Data Sources** ===
34	34
35		-==== **Mandatory Fields for Integration** ====
	37	+Neurodiagnoses maintains an **updated list** of biomedical datasets relevant to neurodegenerative diseases:
36	36
37		-|=Field Name|=Description
38		-|Subject ID|Unique patient identifier
39		-|Diagnosis|Standardized disease classification
40		-|Biomarkers|CSF, plasma, or imaging biomarkers
41		-|Genetic Data|Whole-genome or exome sequencing
42		-|Neuroimaging Metadata|MRI/PET acquisition parameters
	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/]]
43	43
44		-=== **3. Upload Data to Neurodiagnoses** ===
	49	+----
45	45
46		-Once preprocessed, data can be uploaded to EBRAINS or GitHub.
	51	+== **1. Register for Access** ==
47	47
48		-* (((
49		-**Option 1: Upload to EBRAINS Bucket**
	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.
50	50
51		-* Location: [[EBRAINS Neurodiagnoses Bucket>>url:https://wiki.ebrains.eu/bin/view/Collabs/neurodiagnoses/Bucket]]
52		-* Ensure correct metadata tagging before submission.
53		-)))
54		-* (((
55		-**Option 2: Contribute via GitHub Repository**
	57	+----
56	56
57		-* Location: [[GitHub Data Repository>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/tree/main/data]]
58		-* Create a new folder under /data/ and include dataset description.
59		-)))
	59	+== **2. Download & Prepare Data** ==
60	60
61		-//Note: For large datasets, please contact the project administrators before uploading.//
	61	+* Download datasets while adhering to **database usage policies**.
	62	+* Ensure files meet **Neurodiagnoses format requirements**:
62	62
63		-=== **4. Integrate Data into AI Models** ===
	64	+|=**Data Type**|=**Accepted Formats**
	65	+|**Tabular Data**|.csv, .tsv
	66	+|**Neuroimaging**|.nii, .dcm
	67	+|**Genomic Data**|.fasta, .vcf
	68	+|**Clinical Metadata**|.json, .xml
64	64
65		-Once uploaded, datasets must be harmonized and formatted before AI model training.
	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
66	66
67		-==== **Steps for Data Integration** ====
	77	+----
68	68
69		-* Open Jupyter Notebooks on EBRAINS to run preprocessing scripts.
70		-* Standardize neuroimaging and biomarker formats using harmonization tools.
71		-* Use machine learning models to handle missing data and feature extraction.
72		-* Train AI models with newly integrated patient cohorts.
73		-* 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]].
	79	+== **3. Upload Data to Neurodiagnoses** ==
74	74
75		-----
	81	+=== **Option 1: Upload to EBRAINS Bucket** ===
76	76
77		-== **Database Sources Table** ==
	83	+* Location: **EBRAINS Neurodiagnoses Bucket**
	84	+* Ensure **correct metadata tagging** before submission.
78	78
79		-=== **Where to Insert This** ===
	86	+=== **Option 2: Contribute via GitHub Repository** ===
80	80
81		-* GitHub: [[docs/data_sources.md>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/data_sources.md]]
82		-* EBRAINS Wiki: Collabs/neurodiagnoses/Data Sources
	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.
83	83
84		-=== **Key Databases for Neurodiagnoses** ===
	92	+----
85	85
86		-|=Database|=Focus Area|=Data Type|=Access Link
87		-|ADNI|Alzheimer's Disease|MRI, PET, CSF, cognitive tests|ADNI
88		-|PPMI|Parkinson’s Disease|Imaging, biospecimens|[[PPMI>>url:https://www.ppmi-info.org/]]
89		-|GP2|Genetic Data for PD|Whole-genome sequencing|[[GP2>>url:https://gp2.org/]]
90		-|Enroll-HD|Huntington’s Disease|Clinical, genetic, imaging|[[Enroll-HD>>url:https://enroll-hd.org/]]
91		-|GAAIN|Alzheimer's & Cognitive Decline|Multi-source data aggregation|[[GAAIN>>url:https://www.gaain.org/]]
92		-|UK Biobank|Population-wide studies|Genetic, imaging, health records|[[UK Biobank>>url:https://www.ukbiobank.ac.uk/]]
93		-|DPUK|Dementia & Aging|Imaging, genetics, lifestyle factors|[[DPUK>>url:https://www.dementiasplatform.uk/]]
94		-|PRION Registry|Prion Diseases|Clinical and genetic data|[[PRION Registry>>url:https://www.prionalliance.org/]]
95		-|DECIPHER|Rare Genetic Disorders|Genomic variants|DECIPHER
	94	+== **4. Integrate Data into AI Models** ==
96	96
97		-If you know a relevant dataset, submit a proposal in [[GitHub Issues>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/issues]].
	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**.
98	98
	101	+**Reference**: See docs/data_processing.md for detailed instructions.
	102	+
99	99	----
100	100
101		-== **Collaboration & Partnerships** ==
	105	+== **AI-Driven Biomarker Categorization** ==
102	102
103		-=== **Where to Insert This** ===
	107	+Neurodiagnoses employs **AI models** for biomarker classification:
104	104
105		-* GitHub: [[docs/collaboration.md>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/docs/collaboration.md]]
106		-* EBRAINS Wiki: Collabs/neurodiagnoses/Collaborations
	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
107	107
108		-=== **Partnering with Data Providers** ===
	114	+----
109	109
110		-Beyond using existing datasets, Neurodiagnoses seeks partnerships with data repositories to:
	116	+== [[image:workflow neurodiagnoses.png]] ==
111	111
112		-* Enable direct API-based data integration for real-time processing.
113		-* Co-develop harmonized AI-ready datasets with standardized annotations.
114		-* Secure funding opportunities through joint grant applications.
	118	+== **Collaboration & Partnerships** ==
115	115
116		-=== **Interested in Partnering?** ===
	120	+=== **Partnering with Data Providers** ===
117	117
118		-If you represent a research consortium or database provider, reach out to explore data-sharing agreements.
	122	+Neurodiagnoses seeks partnerships with data repositories to:
119	119
120		-* Contact: [[info@neurodiagnoses.com>>mailto:info@neurodiagnoses.com]]
	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.
121	121
	128	+**Interested in Partnering?**
	129	+
	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]]
	132	+
122	122	----
123	123
124	124	== **Final Notes** ==
125	125
126		-Neurodiagnoses continuously expands its data ecosystem to support AI-driven clinical decision-making. Researchers and institutions are encouraged to contribute new datasets and methodologies.
	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**.
127	127
128		-For additional technical documentation:
	139	+**For additional technical documentation**:
129	129
130		-* [[GitHub Repository>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses]]
131		-* [[EBRAINS Collaboration Page>>url:https://wiki.ebrains.eu/bin/view/Collabs/neurodiagnoses/]]
	141	+* **GitHub Repository**: [[Neurodiagnoses GitHub>>url:https://github.com/neurodiagnoses]]
	142	+* **EBRAINS Collaboration Page**: [[EBRAINS Neurodiagnoses>>url:https://ebrains.eu/collabs/neurodiagnoses]]
132	132
133		-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.
	144	+**If you experience issues integrating data**, open a **GitHub Issue** or consult the **EBRAINS Neurodiagnoses Forum**.
	145	+
	146	+----
	147	+
	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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