Dalia Mizikovsky

Identifying therapeutic targets in low‐grade serous ovarian carcinomas with no specific molecular profile

Kathleen I. Pishas, Karla J. Cowley, Evanny Marinovic, Martin Köbel et autres

Low-grade serous ovarian carcinoma (LGSOC) is a rare, indolent ovarian cancer subtype with limited effective therapies. Approximately 40% of cases lack canonical MAPK/ERK or PI3K/AKT/mTOR pathway alterations and are classified as having no specific molecular profile (NSMP). These patients have poor responses …

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Epigenomic regulatory programs reveal the latent heterogeneity of complex diseases

Woo Jun Shim, Shaine Chenxin Bao, C. Chow, Sophie Shen et autres

Summary Complex diseases exhibit substantial variation in clinical presentation and outcome despite shared diagnoses. Current genetic models typically represent inherited risk as a single additive liability, obscuring the diverse biological mechanisms through which variants influence disease. Here, we show that disease-associated variants …

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A scalable, multi-resolution consensus clustering approach for prioritizing robust signals from high-throughput screens

Shaine Chenxin Bao, Kathleen I. Pishas, Karla J. Cowley, Qiongyi Zhao et autres

Modern biology increasingly relies on large-scale screening to generate high dimensional datasets with potential to accelerate discovery. However, analysing these complex datasets remains challenging, due to hierarchical biological structure, uncertainty in the true number of groups, and high dimensional noise that confounds …

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Glycaemic variability underlies myocyte dysfunction and myocardial injury risk in diabetes

Yuanzhao Cao, Meredith A. Redd, Jennifer E. Outhwaite, Dalia Mizikovsky et autres

Heart disease is the leading cause of morbidity and mortality in individuals with diabetes, due largely to risks associated with ischaemic injuries such as myocardial infarction (MI). We use human population genetic data to demonstrate that classical cardiovascular disease risk biomarkers, including …

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Protocol-dependent cardiomyocyte states determine disease modelling capacity of human iPSCs

Sophie Shen, Clarissa Tan, Yuanzhao Cao, C. Chow et autres

ABSTRACT Human induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) are widely used to model cardiovascular disease, yet numerous differentiation protocols generate cardiomyocytes with heterogeneous molecular and functional properties, complicating experimental design. Here we systematically compare sixteen commonly used cardiomyocyte differentiation protocols and characterize …

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Analysis of diverse data to infer genetic programs

Dalia Mizikovsky

Conserved facultative heterochromatin across cell types identify regulatory sequences underpinning cell identity and disease

Enakshi Sinniah, Dalia Mizikovsky, Woo Jun Shim, Yassine Souilmi et autres

Cellular diversity is a product of evolution acting to establish divergent gene regulatory programs from a common genome. Here, we use cross-cell-type epigenetic conservation to gain insight into the impact of selective constraints on genome function and phenotypic variation. By comparing chromatin …

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Glycaemic Variability Underlies Myocyte Dysfunction and Myocardial Injury Risk in Diabetes

Yanna Cao, Meredith A. Redd, Jennifer E. Outhwaite, Dalia Mizikovsky et autres

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Unsupervised Variant Clustering Identifies Genetic Subtypes of Disease

Dalia Mizikovsky, Naomi R. Wray, Sonia Shah, Nathan J. Palpant

Abstract Current approaches to identify disease subtypes rely on prior knowledge or external phenotypic references that limit their generalisability across traits. This study presents an unsupervised, phenotype- free framework that analyses the genetic co-occurrence of variants across individuals to identify variant clusters …

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Glycaemic variability underlies myocyte dysfunction and myocardial injury risk in diabetes

Nathan J. Palpant, Yuanzhao Cao, Meredith A. Redd, Jennifer E. Outhwaite et autres

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Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure

Sophie Shen, Tessa Werner, Samuel W. Lukowski, Stacey B. Andersen et autres

Pluripotent stem cells provide a scalable approach to analyse molecular regulation of cell differentiation across developmental lineages. Here, we engineer barcoded induced pluripotent stem cells to generate an atlas of multilineage differentiation from pluripotency, encompassing an eight-day time course with modulation of …

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Epigenetic constraint of cellular genomes evolutionarily links genetic variation to function

Enakshi Sinniah, Dalia Mizikovsky, Woo Jun Shim, C. Chow et autres

Abstract Cellular diversity is a product of evolution acting to drive divergent regulatory programs from a common genome. Here, we use cross-cell-type epigenetic conservation to gain insight into the impact of selective constraints on genome function and phenotypic variation. By comparing chromatin …

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