Chapter 1 General Introduction

1.1 Land Acknowledgement

The Alberta Diabetes Institute IsletCore is located on Treaty 6 territory, a traditional gathering place for diverse Indigenous peoples including the Cree, Blackfoot, Métis, Nakota Sioux, Iroquois, Dene, Ojibway/ Saulteaux/Anishinaabe, Inuit, and many others.

McGill University is situated on the traditional territory of the Kanien’kehà:ka, a of meeting amongst many First Nations including the Kanien’kehá:ka of the Haudenosaunee Confederacy, Huron/Wendat, Abenaki, and Anishinaabeg.

The University of British Columbia is located on the unceded territory of the Coast Salish Peoples, including the territories of the xwməθkwəy̓əm (Musqueam), Skwxwú7mesh (Squamish), Stó:lō and Səl̓ílwətaʔ/Selilwitulh (Tsleil- Waututh) Nations.

Carleton University is located on the homelands of the Wahpekute and Mdewakanton* bands of the Dakota Nation.

1.2 Terms of Use

Users are required to cite the use of this resource in any publication arising from its use or access. This can be done by citing Ewald et al., in preparation and via the following acknowledgement:

“This work includes data and/or analyses from HumanIslets.com funded by the Canadian Institutes of Health Research, JDRF Canada, and Diabetes Canada (5-SRA-2021-1149-S-B/TG 179092) with data from islets isolated by the Alberta Diabetes Institute IsletCore with the support of the Human Organ Procurement and Exchange (HOPE) program, Trillium Gift of Life Network (TGLN), and other Canadian organ procurement organizations with written informed donor consent as approved by the Human Research Ethics Board at the University of Alberta (Pro00013094).”

The HumanIslets tool relies on statistical methods and R packages published by others. We encourage researchers to cite these publications in addition to our manuscript, based on the citations and links provided throughout the tool interface, manuscript methods, and in this Documentation resource.

Data and analysis tools are provided without warranty, and are not for clinical use, and should not be used directly or indirectly to inform clinical diagnoses or treatment decisions. While every effort has been made to ensure the accuracy, integrity, and validity of the data and analyses presented here for research purposes only, users are solely responsible for any results and interpretations.

Because datasets are occasionally updated, which may impact normalization and analyses, users should report the date of web tool access, analysis, and/or data download. To facilitate this, data downloads are provided with a time/date stamp.

1.3 Financial Support

Data collection has been supported by research grants from the Canadian Institutes of Health Research (MacDonald - 186226, 148451; Johnson - 168857), JDRF (MacDonald - 2-SRA-2019-698-S-B; Pepper - 5-CDA-2020-945-A-N), BCCHRI Child Health Integrative Partnership Strategy Funding (Verchere, Levings and Lynn), the National Institutes of Health (MacDonald - U01-DK-120447; MacDonald/Gloyn - U01-DK-123716; Gloyn - U01-DK105535, U01-DK085545, UM-1DK126185), and the Wellcome Trust (Gloyn - 095101, 200837, 098381, 106130, 203141, 203141) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). Proteomics infrastructure and analysis was supported by the UBC Life Sciences 50 Institute, Canada Foundation for Innovation, BC Knowledge Development Fund, and Genome Canada/BC (PRO264). Pepper holds the Canada Research Chair (CRC) in Cell Therapies for Diabetes (CRC-2021-0026) and MacDonald holds the CRC in Islet Biology (CRC-2019-00334).

Some data used in this web tool includes patch-seq data, and single-cell RNAseq used for cell type expression analysis, from the Human Pancreas Analysis Program (HPAP-RRID:SCR_016202) Database(https://hpap.pmacs.upenn.edu), a Human Islet Research Network (RRID:SCR_014393) consortium (UC4-DK-112217, U01-DK-123594, UC4-DK-112232, and U01-DK-123716).

Consolidation of datasets and web tool development was supported by a research grant funded by the Canadian Institutes of Health Research, JDRF Canada, and Diabetes Canada (5-SRA-2021-1149-S-B/TG 179092) to MacDonald (Alberta), Xia (McGill), Johnson (UBC) and Bruin (Carleton) with collaborators Gloyn (Stanford), Foster (UBC), Atlas (Ottawa), Mulvihill (Ottawa), Lynn (UBC), and Verchere (UBC).

1.4 Overview and Sample/data Collection

The purpose of the HumanIslets.com tool is to allow exploration and analysis of, and access to data from, human islet molecular and functional phenotyping studies. We hope this resource will facilitate research and hypothesis generation in a manner that is accessible to both experts and non-experts in data analysis. The below figure illustrates general workflows, samples, and datasets collected as part of this initiative Data noted in blue are currently included within the web tool, while those in grey are are planned for addition at a later date.