Eleven grand challenges in single-cell data science

Genome biology, Journal Year: 2020, Volume and Issue: 21(1)

Published: Feb. 7, 2020

Abstract The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell technology. Thousands—or even millions—of cells analyzed a single experiment amount to data revolution biology pose unique science problems. Here, we outline eleven challenges that will be central bringing this emerging field of forward. For each challenge, highlight motivating research questions, review prior work, formulate open This compendium is for established researchers, newcomers, students alike, highlighting interesting rewarding problems the coming years.

Language: Английский

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Machine learning approaches to drug response prediction: challenges and recent progress

npj Precision Oncology, Journal Year: 2020, Volume and Issue: 4(1)

Published: June 15, 2020

Abstract Cancer is a leading cause of death worldwide. Identifying the best treatment using computational models to personalize drug response prediction holds great promise improve patient’s chances successful recovery. Unfortunately, task predicting very challenging, partially due limitations available data and algorithmic shortcomings. The recent advances in deep learning may open new chapter search for ultimately result more accurate tools therapy response. This review provides an overview challenges prediction, focuses on comparing machine techniques be utmost practical use clinicians non-experts. incorporation modalities such as single-cell profiling, along with that rapidly find effective combinations will likely instrumental improving cancer care.

Language: Английский

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Tumor evolution: Linear, branching, neutral or punctuated?

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2017, Volume and Issue: 1867(2), P. 151 - 161

Published: Jan. 19, 2017

Language: Английский

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Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 22(1), P. 3 - 18

Published: Aug. 17, 2020

Language: Английский

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Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Oct. 21, 2020

Abstract Clonal diversity is a consequence of cancer cell evolution driven by Darwinian selection. Precise characterization clonal architecture essential to understand the evolutionary history tumor development and its association with treatment resistance. Here, using single-cell DNA sequencing, we report mutational histories 123 acute myeloid leukemia (AML) patients. The data reveals cell-level mutation co-occurrence enables reconstruction characterized linear branching patterns evolution, latter including convergent evolution. Through xenotransplantion, show initiating capabilities individual subclones evolving in parallel. Also, simultaneous surface protein analysis, illustrate both genetic phenotypic AML. Lastly, analysis longitudinal samples underlying process therapeutic Together, these unravel AML, highlight their clinical relevance era precision medicine.

Language: Английский

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The evolution of tumour phylogenetics: principles and practice

Nature Reviews Genetics, Journal Year: 2017, Volume and Issue: 18(4), P. 213 - 229

Published: Feb. 13, 2017

Language: Английский

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Unravelling Intratumoral Heterogeneity through High-Sensitivity Single-Cell Mutational Analysis and Parallel RNA Sequencing

Molecular Cell, Journal Year: 2019, Volume and Issue: 73(6), P. 1292 - 1305.e8

Published: Feb. 12, 2019

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving transcriptional heterogeneity. However, its application to studying cancerous tissues is currently hampered by the lack of coverage across key mutation hotspots in vast majority cells; this prevents correlation genetic and readouts from same single cell. To overcome this, we developed TARGET-seq, method high-sensitivity detection multiple mutations within cells both genomic coding DNA, parallel with unbiased whole-transcriptome analysis. Applying TARGET-seq 4,559 cells, demonstrate how technique uniquely resolves tumor heterogeneity myeloproliferative neoplasms (MPN) stem progenitor providing insights into deregulated pathways mutant non-mutant cells. molecular signatures genetically distinct subclones cancer

Language: Английский

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The longitudinal dynamics and natural history of clonal haematopoiesis

Nature, Journal Year: 2022, Volume and Issue: 606(7913), P. 335 - 342

Published: June 1, 2022

Abstract Clonal expansions driven by somatic mutations become pervasive across human tissues with age, including in the haematopoietic system, where phenomenon is termed clonal haematopoiesis 1–4 . The understanding of how and when develops, factors that govern its behaviour, it interacts ageing these variables relate to malignant progression remains limited 5,6 Here we track 697 clones from 385 individuals 55 years age or older over a median 13 years. We find 92.4% expanded at stable exponential rate study period, different driving substantially growth rates, ranging 5% ( DNMT3A TP53 ) more than 50% per year SRSF2 P95H ). Growth rates same mutation differed approximately ±5% year, proportionately affecting slow drivers substantially. By combining our time-series data phylogenetic analysis 1,731 whole-genome sequences colonies 7 an group, reveal distinct patterns lifelong behaviour. -mutant preferentially early life displayed slower old context increasingly competitive oligoclonal landscape. contrast, splicing gene drove expansion only later life, whereas TET2 emerged all ages. Finally, show faster carry higher risk progression. Our findings characterize natural history give fundamental insights into interactions between mutation, selection.

Language: Английский

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Single-cell DNA sequencing reveals a late-dissemination model in metastatic colorectal cancer

Genome Research, Journal Year: 2017, Volume and Issue: 27(8), P. 1287 - 1299

Published: May 25, 2017

Metastasis is a complex biological process that has been difficult to delineate in human colorectal cancer (CRC) patients. A major obstacle understanding metastatic lineages the extensive intra-tumor heterogeneity at primary and tumor sites. To address this problem, we developed highly multiplexed single-cell DNA sequencing approach trace of two CRC patients with matched liver metastases. Single-cell copy number or mutational profiling was performed, addition bulk exome targeted deep-sequencing. In first patient, observed monoclonal seeding, which single clone evolved large mutations prior migrating establish tumor. second polyclonal independent clones seeded after having diverged different time points from lineage. The data also revealed an unexpected lineage did not metastasize, early progenitor “first hit” mutation APC subsequently gave rise both tumors. Collectively, these reveal late-dissemination model metastasis provide unprecedented view genomic resolution.

Language: Английский

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Understanding tumor ecosystems by single-cell sequencing: promises and limitations

Genome biology, Journal Year: 2018, Volume and Issue: 19(1)

Published: Dec. 1, 2018

Cellular heterogeneity within and across tumors has been a major obstacle in understanding treating cancer, the complex is masked if bulk tumor tissues are used for analysis. The advent of rapidly developing single-cell sequencing technologies, which include methods related to genome, epigenome, transcriptome, multi-omics sequencing, have applied cancer research led exciting new findings fields evolution, metastasis, resistance therapy, microenvironment. In this review, we discuss recent advances limitations these technologies their potential applications studies.

Language: Английский

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