Data for: Principles of subclonal gene dosage across human cancers
https://doi.org/10.48723/gr42-ja30
The data shared here are joint single-cell Whole genome sequencing (WGS) and single-cell mRNA sequencing from primary patient material from different cancer types. Primary samples from pediatric acute lymphoblastic leukemias, acute myeloid leukemias, breast cancers, melanomas and sarcomas were processed using Direct nuclear tagmentation and RNA-sequencing (DNTR-seq). For more information on DNTR-seq, see ‘A Highly Scalable Method for Joint Whole-Genome Sequencing and Gene-Expression Profiling of Single Cells’, DOI:10.1016/j.molcel.2020.09.025.
Data shared here are the fastq files of all single cells sequenced in this study (21826 read 1 and 21826 read 2 files).
The size of the dataset is approximately 2 TB.
Files with open access (2)
Files with open access (2)
Citation and access
Citation and access
Access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
Yes
Type of personal data:
Data are WGS and mRNA sequencing data from single cells from patients with cancer (both cancer and normal cells were sequenced)
Code key exists:
Yes
Sensitive personal data:
Yes
Citation:
Language:
Method and outcome
Method and outcome
Population:
The group of samples come from cancer patients diagnosed in Swedish hospitals. The cancer patients had been diagnosed with pediatric acute lymphoblastic leukemia (n:15), acute myeloid leukemia (n:5), melanoma (n:2), sarcomas (n:11) or breast cancer (n:11).
Time method:
Study design:
- Preclinical study
Description of study design:
Samples from cancer patients were collected through bone marrow sampling (leukemias) or after surgical resection (solid tumours). Bone marrow samples were depleted of red blood cells and stored in FBS+10%DMSO until further processing. Surgically resected tumors were enzymatically and mechanically dissociated before being stored in FBS+10%DMSO.
Samples were then processed by performing dead cell removal, and antibody staining to enrich for tumor cells by flow cytometry. Single cells (~500 per patient) were sorted into 384 well plates and the plates were processed using DNTR-seq, see "A Highly Scalable Method for Joint Whole-Genome Sequencing and Gene-Expression Profiling of Single Cells" at doi:10.1016/j.molcel.2020.09.025, which enables WGS and mRNA sequencing on individual cells.
Data was analyzed using ASCENT (Absolute Single cell Copy number Evaluation and subcloNe Topology), described thoroughly in "Absolute copy number aware CNV calling of sub-megabase segments in ultra-low coverage single-cell DNA sequencing data", see doi:https://doi.org/10.1093/nar/gkaf919, enabling the study of genetic clones, identified by CNVs (Copy number variations) and their expression patterns.
Description of sampling:
We selected different cancer types, known to have different levels and types of CNVs for this study. This included pediatric acute lymphoblastic leukemia (known to have few but large CNVs) acute myeloid leukemia (large CNVs), melanoma (mainly characterized by Single nucleotide variants, SNVs) or breast cancer (multiple small and large CNVs). The leukemia samples originated from bone marrow aspirations taken at diagnosis of the disease. Breast cancer and sarcoma samples originate from surgical resection (without neoadjuvant treatment), following diagnosis. The melanoma samples were metastatic and originated from surgical resections.
Number of individuals/objects:
44
Data format/data structure:
Geographic coverage
Geographic coverage
Geographic location:
Administrative information
Administrative information
Responsible department/unit:
Department of Oncology-Pathology [K7]
Other research principals:
Contributor(s):
- Karolinska Institutet – Department of Women’s and Children’s Health
Ethical Review
Ethical Review
Reviewer:
- Swedish Ethical Review Authority
Opens a new window at ror.org.
ROR
Registration number:
Dnr 2024-02994-01
Ethical review information:
Molekylär karakterisering av avancerat malignant melanom för att identifiera biomarkörer av betydelse för sjukdomens prognos
Reviewer:
- Swedish Ethical Review Authority
Opens a new window at ror.org.
ROR
Registration number:
Dnr 2022-04838-02
Ethical review information:
Ex vivo tumörmodeller för behandling och translationell forskning (bröstcancer)
Reviewer:
- Swedish Ethical Review Authority
Opens a new window at ror.org.
ROR
Registration number:
Dnr 2019-01805
Ethical review information:
Karaktärisesring av läkemedelsresistensmekanismer vid akut myeloisk leukemi hos barn och vuxna
Reviewer:
- Swedish Ethical Review Authority
Opens a new window at ror.org.
ROR
Registration number:
Dnr 2021-02718
Ethical review information:
Analys av genetiska förändringar och genuttryck vid akut lymfatisk leukemi hos barn
Reviewer:
- Swedish Ethical Review Authority
Opens a new window at ror.org.
ROR
Registration number:
2025-06780-01
Funding
Funding
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2023-02912
Funding agency:
- The Swedish Cancer Society
Opens a new window at ror.org.
ROR
Award number:
232839 Pj
Funding agency:
- Swedish Childhood Cancer Foundation
Opens a new window at ror.org.
ROR
Award number:
PR2024-0108 and MT2023-0014
Topic and keywords
Topic and keywords
CESSDA topic classification:
Swedish Standard Classification of Research Subjects 2025:
Publications
Publications
Citation:
Kolbeinsdottir, S., Zachariadis, V., Sommerauer, C., Lohi, O., Heinaniemi, M., & Enge, M. (2025). Absolute copy number aware CNV calling of sub-megabase segments in ultra-low coverage single-cell DNA sequencing data. In NUCLEIC ACIDS RESEARCH (Vol. 53, Issue 17). https://doi.org/10.1093/nar/gkaf919
DOI:
SwePub:
Citation:
Zachariadis, V., Cheng, H., Andrews, N., & Enge, M. (2020). A Highly Scalable Method for Joint Whole-Genome Sequencing and Gene-Expression Profiling of Single Cells. In MOLECULAR CELL (Vol. 80, Issue 3, pp. 541-553.e5). https://doi.org/10.1016/j.molcel.2020.09.025
