#  DATA COLLECTION

Describe for all the data that will be collected the collection procedure in
as much detail as possible including where possible pictures images etc.

##  • Mouse RNA-seq data

Mouse tissue from the esophagus and the large intestine will be isolated from
healthy and diseased mice and will be processed for the generation of RNA,
which will be used from the generation of sequencing libraries to be run in
the Illumina NextSeq 500 sequencer within the Greek genome Center at BRFAA.
Raw data will be processed with the use of appropriate algorithms and
comparison will be performed between healthy tissues and diseased tissues at
various stages of the disease. Molecular biomarkers that discriminate between
the healthy and diseased state will be identified.

##  • Optical data from mice and human tissues

Mouse tissue from the esophagus and the large intestine from healthy and
diseased mice and human specimen collected at UMCG will be imaged with the
hybrid Raman/Scattering microscope (see Fig. 1 for the designs of the
microscope), as well as the existing SHG, THG, and OA microscope at HMGU.
Specific acquisition protocols will ensure imaging of the same tissue regions
with both microscopes. Raw data will be processed with the use of appropriate
algorithms and comparison will be performed between healthy tissues and
diseased tissues at various stages of the disease. Molecular biomarkers that
discriminate between the healthy and diseased state will be identified in
combination with the RNA-seq analysis.

**Fig. 1.** Designs of the (a) Raman and (b) scattering modules as coupled in
the hybrid microscope.

##  • Clinical validation of the endoscope on patients

**_Adenoma trial in high risk colorectal cancer Lynch syndrome (LS) patients_
** : We will perform SRS/Scattering endoscopy of the rectum to identify
patients with adenomas and the accompanying field cancerization fingerprints
with guidance of standard surveillance colonoscopy. Results will be compared
with the amount of detected adenomas in these patients and degree of standard
histopathology. On average, 30-50% of the Lynch patients will have 1 or more
polyps during colonoscopy. The patient without adenomas will serve as
controls. Control biopsies of normal tissue will be collected for ex vivo
control.

**_Barrett trial in patients with early stage esophageal cancer_ ** :
SRS/Scattering endoscopy will be performed on patients with dysplasia or early
stage esophageal cancer patients, who are scheduled for endoscopic mucosal
resection (EMR). As control, we will include Barrett patients undergoing
surveillance endoscopy without dysplastic lesions. Field cancerization
alterations will be assessed in the normal adjacent Barrett epithelium.
Control biopsies of normal tissue will be collected for ex vivo control.

The hybrid SRS/Scattering endoscope will consist of two polarization-
maintaining fibers for scattering (illumination/collection) and one excitation
and a number of collection fibers for SRS spectroscopy. Before in vivo human
application, the endoscope will undergo constancy and mechanical integrity
tests against repeat standard clinical washing procedures. The number, type,
and distribution of fibers will be determined during the design and validation
of the test probes and will be based on the findings from the multimodal
microscope, as well as on the clinical needs. Finally, the developed endoscope
will follow the “motherdaughter” approach, where it will be passed through the
working channel of a normal endoscope (figure 2) and thus be used during
normal surveillance colonoscopy/endoscopy procedures.

**Figure 2 Design of standard gastrointestinal endoscope (GIF-H190) that is
currently used as a standard endoscope in the UMCG. Images adapted from EVIS
EXERA III gastrovideoscope brochure.**

#  DATA MANAGEMENT

SENSITIVE participates in the Open Research Data Pilot (ORDP) which aims to
improve access to and re-use of research data generated by Horizon 2020
projects and applies primarily to the data needed to validate the results
presented in scientific publications.

To support the FAIR principles, SENSITIVE is oriented towards the Zenodo
solution. Zenodo is built and developed by researchers, for Open Science. The
OpenAIRE project, for open access and open data movements in Europe was
commissioned by the EC to support their nascent Open Data policy by providing
a catch-all repository for EC funded research. CERN, an OpenAIRE partner and
pioneer in open source, open access and open data, provided this capability
and Zenodo was launched 2013. In support of its research programme CERN has
developed tools for Big Data management and extended Digital Library
capabilities for Open Data. Through Zenodo these Big Science tools could be
effectively shared with the long-tail of research.

For **findable** data, Zenodo provides a Digital Object Identifier (DOI),
which is issued to every published record. Zenodo's metadata is compliant with
DataCite's Metadata Schema m  inimum and recommended terms, with a few
additional enrichements. The DOI is a top-level and a mandatory field in the
metadata of each record. Metadata of each record is indexed and searchable
directly in Zenodo's search engine immediately after publishing. Metadata of
each record is sent to DataCite servers during DOI registration and indexed
there.

For making data openly **accessible** Zenodo provides metadata for individual
records as well as record collections are harvestable using the OAI- PMH
protocol by the record identifier and the collection name. Metadata is also
retrievable through the public REST API. OAI-PMH and REST are open, free and
universal protocols for information retrieval on the web. Metadata are
publicly accessible and licensed under public domain. No authorization is ever
necessary to retrieve it. Data and metadata will be retained for the lifetime
of the repository.

For making data **interoperable** Zenodo provides a formal, accessible,
shared, and broadly applicable meta(data) language. Zenodo uses JSON Schema as
internal representation of metadata and offers export to other popular formats
such as Dublin Core or MARCXML. Each referenced external piece of metadata is
qualified by a resolvable URL.

For making data **re-useable** in Zenodo each record contains a minimum of
DataCite's mandatory terms, with optionally additional DataCite recommended
terms and Zenodo's enrichments. License is one of the mandatory terms in
Zenodo's metadata and is referring to an Open Definition license. Data
downloaded by the users is subject to the license specified in the metadata by
the uploader. All data and metadata uploaded is tracable to a registered
Zenodo user. Metadata can optionally describe the original authors of the
published work. Zenodo is not a domain-specific repository, yet through
compliance with DataCite's Metadata Schema, metadata meets one of the broadest
crossdomain standards available.

#  DATA SECURITY / SHARING

Guidelines for data security and personal data protection will be followed. To
protect data storage and processing, the following safety measures will be
undertaken:

  * Compliance with the **General Data Protection Regulation** – (EU) 2016/679 (EU **GDPR** ) 

  

  * Reporting of data security incidents including personal data breach to data controller of the related dataset within two working days after becoming aware of it. 

  

The datasets should be shared with all partners once all relevant legal
procedures (informed consent, CDA, MTA, ethical approval) are in place.

The informed consent of study participants will cover the sharing of data
collected directly from the study participant and/or based on the measurement
of the derived bio-samples from the study participant. Even though every
effort will be made to keep data confidential, there is a possibility that
information can be linked to the individual. We will inform the research
subject about this possibility and respect his decision, if he/she wishes to
completely anonymise his/her data.

#  ETHICAL ASPECTS

All research activities performed for the collection, use, transfer and
protection of patient data, including biological samples will follow the
ethical standards and guidelines of Horizon 2020 including the Charter of
Fundamental Rights of the European Union and the European Convention on Human
Rights. Patients’ data and biological samples will be lawfully collected and
processed. Medical research in human subjects will follow the procedures
described in the World Medical Association’s Declaration of Helsinki and the
Oviedo Bioethics Convention (Convention on Human Rights and Biomedicine). In
addition, all procedures will comply with National law and the European
Union’s General Data Protection Regulation  (GDPR)  . Collection, use, storage
and otherwise processing of human genetic data, human proteomic data and of
the biological samples from which they are derived will comply with UNESCO's
Universal Declaration on the Human Genome and Human Rights and International
Declaration on Human Genetic Data.

All SENSITIVE partners confirm that the ethical standards and guidelines of
Horizon 2020 will be rigorously applied, regardless of the country in which
the research is carried out. No studies will commence before the approval of
relevant ethics committee has been obtained where such an approval is
required. Biomedical research will comply with international and EU
conventions and declarations. Appropriate informed consent form is a
prerequisite for obtaining approval. Informed consent procedures and data
processing, including data/sample collection, and use, data transfers, storage
and security will comply with the new EU’s General Data Protection Regulation.

All data related processes, from collection and sharing to data research and
sustainability will be in compliance with the legal requirements established
by GDPR (General Data Protection Regulation).

#  CONCLUSION

This is the first version of the SENSITIVE Data Management Plan. The plan
follows the Horizon 2020guidelines for findable, accessible, interoperable and
reusable (FAIR) data and will address the EU’s General Data Protection
Regulation (GDPR). The project participates in the Open Research Data Pilot
(ORDP), which aims to improve access to and re-use of research data generated
by Horizon 2020 projects and applies primarily to the data needed to validate
the results presented in scientific publications. The SENSITIVE DMP is
intended to be a “living document” and will be updated in the context of the
periodic reporting of the project.