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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**.
	1	+== **Overview** ==
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	+
3	3	----
4	4
5		-== **Neurodiagnoses AI: Multimodal AI for Neurodiagnostic Predictions** ==
	7	+== **How to Use External Databases in Neurodiagnoses** ==
6	6
7		-=== **Project Overview** ===
	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.
8	8
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**.
	11	+=== **Potential Data Sources** ===
10	10
11		-== **Neuromarker: Generalized Biomarker Ontology** ==
	13	+Neurodiagnoses maintains an updated list of potential biomedical databases relevant to neurodegenerative diseases.
12	12
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**.
	15	+* Reference: [[List of Potential Databases>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/blob/main/data/sources/list_of_potential_databases]]
14	14
15		-=== **Core Biomarker Categories** ===
	17	+=== **1. Register for Access** ===
16	16
17		-The following ontology is used within **Neurodiagnoses AI** for biomarker categorization:
	19	+Each external database requires individual registration and access approval. Follow the official guidelines of each database provider.
18	18
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
	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.
28	28
29		-----
	24	+=== **2. Download & Prepare Data** ===
30	30
31		-== **How to Use External Databases in Neurodiagnoses** ==
	26	+Once access is granted, download datasets while complying with data usage policies. Ensure that the files meet Neurodiagnoses’ format requirements for smooth integration.
32	32
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.
	28	+==== **Supported File Formats** ====
34	34
35		-=== **Potential Data Sources** ===
	30	+* Tabular Data: .csv, .tsv
	31	+* Neuroimaging Data: .nii, .dcm
	32	+* Genomic Data: .fasta, .vcf
	33	+* Clinical Metadata: .json, .xml
36	36
37		-Neurodiagnoses maintains an **updated list** of biomedical datasets relevant to neurodegenerative diseases:
	35	+==== **Mandatory Fields for Integration** ====
38	38
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/]]
	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
48	48
49		-----
	44	+=== **3. Upload Data to Neurodiagnoses** ===
50	50
51		-== **1. Register for Access** ==
	46	+Once preprocessed, data can be uploaded to EBRAINS or GitHub.
52	52
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.
	48	+* (((
	49	+**Option 1: Upload to EBRAINS Bucket**
56	56
57		-----
	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**
58	58
59		-== **2. Download & Prepare Data** ==
	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	+)))
60	60
61		-* Download datasets while adhering to **database usage policies**.
62		-* Ensure files meet **Neurodiagnoses format requirements**:
	61	+//Note: For large datasets, please contact the project administrators before uploading.//
63	63
64		-|=**Data Type**|=**Accepted Formats**
65		-|**Tabular Data**|.csv, .tsv
66		-|**Neuroimaging**|.nii, .dcm
67		-|**Genomic Data**|.fasta, .vcf
68		-|**Clinical Metadata**|.json, .xml
	63	+=== **4. Integrate Data into AI Models** ===
69	69
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
	65	+Once uploaded, datasets must be harmonized and formatted before AI model training.
76	76
77		-----
	67	+==== **Steps for Data Integration** ====
78	78
79		-== **3. Upload Data to Neurodiagnoses** ==
	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]].
80	80
81		-=== **Option 1: Upload to EBRAINS Bucket** ===
82		-
83		-* Location: **EBRAINS Neurodiagnoses Bucket**
84		-* Ensure **correct metadata tagging** before submission.
85		-
86		-=== **Option 2: Contribute via GitHub Repository** ===
87		-
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.
91		-
92	92	----
93	93
94		-== **4. Integrate Data into AI Models** ==
	77	+== **Database Sources Table** ==
95	95
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**.
	79	+=== **Where to Insert This** ===
100	100
101		-**Reference**: See docs/data_processing.md for detailed instructions.
	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
102	102
103		-----
	84	+=== **Key Databases for Neurodiagnoses** ===
104	104
105		-== **AI-Driven Biomarker Categorization** ==
	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
106	106
107		-Neurodiagnoses employs **AI models** for biomarker classification:
	97	+If you know a relevant dataset, submit a proposal in [[GitHub Issues>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses/issues]].
108	108
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
113		-
114	114	----
115	115
116		-== [[image:workflow neurodiagnoses.png]] ==
117		-
118	118	== **Collaboration & Partnerships** ==
119	119
	103	+=== **Where to Insert This** ===
	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
	107	+
120	120	=== **Partnering with Data Providers** ===
121	121
122		-Neurodiagnoses seeks partnerships with data repositories to:
	110	+Beyond using existing datasets, Neurodiagnoses seeks partnerships with data repositories to:
123	123
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.
	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.
127	127
128		-**Interested in Partnering?**
	116	+=== **Interested in Partnering?** ===
129	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]]
	118	+If you represent a research consortium or database provider, reach out to explore data-sharing agreements.
132	132
	120	+* Contact: [[info@neurodiagnoses.com>>mailto:info@neurodiagnoses.com]]
	121	+
133	133	----
134	134
135	135	== **Final Notes** ==
136	136
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**.
	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.
138	138
139		-**For additional technical documentation**:
	128	+For additional technical documentation:
140	140
141		-* **GitHub Repository**: [[Neurodiagnoses GitHub>>url:https://github.com/neurodiagnoses]]
142		-* **EBRAINS Collaboration Page**: [[EBRAINS Neurodiagnoses>>url:https://ebrains.eu/collabs/neurodiagnoses]]
	130	+* [[GitHub Repository>>url:https://github.com/Fundacion-de-Neurociencias/neurodiagnoses]]
	131	+* [[EBRAINS Collaboration Page>>url:https://wiki.ebrains.eu/bin/view/Collabs/neurodiagnoses/]]
143	143
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.
	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.

workflow neurodiagnoses.png

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