Alan Murphy

• Imperial College London

Introductory paragraph Panic attacks, sudden episodes of intense fear accompanied by physical and psychological symptoms, affect approximately 23% of the population 1,2 . Panic disorder, diagnosed in 2– 4% ³ , involves recurrent attacks followed by persistent worry about further attacks, leading to functional impairment and avoidance behaviours 1,2...

To understand the complex relationship between histone mark activity and gene expression, recent advances have used in silico predictions based on large-scale machine learning models. However, these approaches have omitted key contributing factors like cell state, histone mark function or distal effects, which impact the relationship, limiting thei...

Understanding how genetic variants affect the epigenome is key to interpreting GWAS, yet profiling these effects across the non-coding genome remains challenging due to experimental scalability. This necessitates accurate computational models. Existing machine learning approaches, while progressively improving, are confined to the cell types they w...

To understand the complex relationship between histone mark activity and gene expression, recent advances have used in silico predictions based on large-scale machine learning models. However, these approaches have omitted key contributing factors like cell state, histone mark function or distal effects, that impact the relationship, limiting their...

Understanding genetic variants effects on the epigenome is crucial for interpreting genome-wide association studies (GWAS) results, yet profiling these effects across the non-coding genome remains challenging due to the scalability limits of experimental methods. This necessitates accurate computational models. Existing machine learning approaches,...

Despite calls to improve reproducibility in research, achieving this goal remains elusive even within computational fields. Currently, >50% of R packages are distributed exclusively through GitHub. While the trend towards sharing open-source software has been revolutionary, GitHub does not have any default built-in checks for minimal coding standar...

Mathys et al. conducted the first single-nucleus RNA-seq (snRNA-seq) study of Alzheimer’s disease (AD) (Mathys et al., 2019). With bulk RNA-seq, changes in gene expression across cell types can be lost, potentially masking the differentially expressed genes (DEGs) across different cell types. Through the use of single-cell techniques, the authors b...

Mathys et al., conducted the first single-nucleus RNA-Seq study (snRNA-Seq) of Alzheimer’s disease (AD)1. The authors profiled the transcriptomes of approximately 80,000 cells from the prefrontal cortex, collected from 48 individuals – 24 of which presented with varying degrees of AD pathology. With bulk RNA-Seq, changes in gene expression across c...

Arising From Mathys, H. et al. Nature (2019). https://doi.org/10.1038/s41586-019-1195-2 Mathys et al., conducted the first single-nucleus RNA-Seq study (snRNA-Seq) of Alzheimer’s disease (AD)1. The authors profiled the transcriptomes of approximately 80,000 cells from the prefrontal cortex, collected from 48 individuals – 24 of which presented with...

Mathys, H. et al. Nature (2019). https://doi.org/10.1038/s41586-019-1195-2 Mathys et al., conducted the first single-nucleus RNA-Seq study (snRNA-Seq) of Alzheimer’s disease (AD) 1 . The authors profiled the transcriptomes of approximately 80,000 cells from the prefrontal cortex, collected from 48 individuals – 24 of which presented with varying de...

EpiCompare combines a variety of downstream analysis tools to compare, quality control and benchmark different epigenomic datasets. The package requires minimal input from users, can be run with just one line of code and provides all results of the analysis in a single interactive HTML report. EpiCompare thus enables downstream analysis of multiple...

Arising From: Mathys, H. et al. Nature (2019). https://doi.org/10.1038/s41586–019–1195–2 Mathys et al., conducted the first single-nucleus RNA-Seq study (snRNA–Seq) of Alzheimer′s disease (AD). The authors profiled the transcriptomes of approximately 80,000 cells from the prefrontal cortex, collected from 48 individuals – 24 of which presented with...

Reproducibility is essential to the progress of research, yet achieving it remains elusive even in computational fields. Continuous Integration (CI) platforms offer a powerful way to launch automated workflows to check and document code, but often require considerable time, effort, and technical expertise to setup. We therefore developed the rworkf...

Leigh syndrome is a rare inherited, complex, neurometabolic disorder with genetic and clinical heterogeneity. Features present in affected patients range from classical stepwise developmental regression to ataxia, seizures, tremor, and occasionally psychiatric manifestations. Currently, more than 100 monogenic causes of Leigh syndrome have been ide...

Leigh syndrome (subacute necrotising encephalomyelopathy) is a rare inherited, complex, and typically early onset mitochondrial disorder with clinical and genetic heterogeneity. It owes its heterogeneous nature to the complex nature of mitochondrial genetics and the significant interactions that occur between the mitochondrial and nuclear genomes....

EpiCompare combines a variety of downstream analysis tools to compare, quality control and benchmark different epigenomic datasets. The package requires minimal input from users, can be run with just one line of code and provides all results of the analysis in a single interactive HTML report. EpiCompare thus enables downstream analysis of multiple...

Arising From Zimmerman, K. D., Espeland, M. A. & Langefeld, C. D. Nature Communications (2021). https://doi.org/10.1038/s41467-021-21038-1 Summary Recently, Zimmerman et al ., ¹ proposed the use of mixed models over pseudobulk aggregation approaches, reporting improved performance on a novel simulation approach of hierarchical single-cell expressi...

The amount of any given protein in the brain is determined by the rates of its synthesis and destruction, which are regulated by different cellular mechanisms. Here, we combine metabolic labelling in live mice with global proteomic profiling to simultaneously quantify both the flux and amount of proteins in mouse models of neurodegeneration. In mul...

Motivation Genome-wide association studies (GWAS) summary statistics have popularised and accelerated genetic research. However, a lack of standardisation of the file formats used has proven problematic when running secondary analysis tools or performing meta-analysis studies. Results To address this issue, we have developed MungeSumstats, a Bioco...

Advances in single-cell RNA-sequencing technology over the last decade have enabled exponential increases in throughput: datasets with over a million cells are becoming commonplace. The burgeoning scale of data generation, combined with the proliferation of alternative analysis methods, led us to develop the scFlow toolkit and the nf-core/scflow pi...

Advances in single-cell RNA-sequencing technology over the last decade have enabled exponential increases in throughput: datasets with over a million cells are becoming commonplace. The burgeoning scale of data generation, combined with the proliferation of alternative analysis methods, led us to develop the scFlow toolkit and the nf-core/scflow pi...

Advances in single-cell RNA-sequencing technology over the last decade have enabled exponential increases in throughput: datasets with over a million cells are becoming commonplace. The burgeoning scale of data generation, combined with the proliferation of alternative analysis methods, led us to develop the scFlow toolkit and the nf-core/scflow pi...

Genome-wide association studies (GWAS) summary statistics have democratised and accelerated genetic research. However, a lack of standardisation of the file formats used has proven problematic when running secondary analysis tools or performing meta-analysis studies. To address these issues, we have developed MungeSumstats, a Bioconductor R package...