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Bartlett, T. E.

Publications and source records attributed to Bartlett, T. E..

2 recordsLinked to original sources

Fusion of single-cell transcriptome and DNA-binding data, for genomic network inference in cortical development

BackgroundNetwork models are well-established as very useful computational-statistical tools in cell biology. However, a genomic network model based only on gene expression data can, by definition, only infer gene co-expression networks. Hence, in order to infer gene regulatory patterns, it is necessary to also include data related to binding of regulatory factors to DNA. ResultsWe propose a new dynamic genomic network model, for inferring patterns of genomic regulatory influence in dynamic processes such as development. Our model fuses experiment-specific gene expression data with publicly available DNA-binding data. The method we propose is computationally efficient, and can be applied to genome-wide data with tens of thousands of transcripts. Thus, our method is well suited for use as an exploratory tool for genome-wide data. We apply our method to data from human fetal cortical development, and our findings confirm genomic regulatory patterns which are recognised as being fundamental to neuronal development. ConclusionsOur method provides a mathematical/computational toolbox which, when coupled with targeted experiments, will reveal and confirm important new functional genomic regulatory processes in mammalian development.

bioinformatics↗

Inference of tissue relative proportions of the breast epithelial cell types luminal progenitor, basal, and luminal mature

Single-Cell Analysis has revolutionised genomic science in recent years. However, due to cost and other practical considerations, single-cell analyses are impossible for studies based on medium or large patient cohorts. For example, a single-cell analysis usually costs thousands of euros for one tissue sample from one volunteer, meaning that typical studies using single-cell analyses are based on very few individuals. While single-cell genomic data can be used to examine the phenotype of individual cells, cell-type deconvolution methods are required to track the quantities of these cells in bulk-tissue genomic data. Hormone receptor negative breast cancers are highly aggressive, and are thought to originate from a subtype of epithelial cells called the luminal progenitor. In this paper, we show how to quantify the number of luminal progenitor cells as well as other epithelial subtypes in breast tissue samples using DNA and RNA based measurements. We find elevated levels of cells which resemble these hormone receptor negative luminal progenitor cells in breast tumour biopsies of hormone receptor negative cancers, as well as in healthy breast tissue samples from BRCA1 (FANCS) mutation carriers. We also find that breast tumours from carriers of heterozygous mutations in non-BRCA Fanconi Anaemia pathway genes are much more likely to be hormone receptor negative. These findings have implications for understanding hormone receptor negative breast cancers, and for breast cancer screening in carriers of heterozygous mutations of Fanconi Anaemia pathway genes.

bioinformatics↗