Piotr Grabowski

AstraZeneca | AZ

Operons are transcriptional modules that allow bacteria to adapt to environmental changes by coordinately expressing the relevant set of genes. In humans, biological pathways and their regulation are more complex. If and how human cells coordinate the expression of entire biological processes is unclear. Here, we capture 31 higher-order co-regulati...

The mechanisms of coordinated changes in proteome composition and their relevance for the differentiation of neutrophil granulocytes are not well studied. Here, we discover two novel human genetic defects in SRPRA and SRP19, constituents of the mammalian co-translational targeting machinery and characterize their role in neutrophil granulocyte diff...

Artificial intelligence recently experienced a renaissance with the advancement of convolutional neural networks (CNNs). CNNs require spatially meaningful matrices (e.g., image data) with recurring patterns, limiting its applicability to high-throughput omics data. We present GIM, a simple, CNN-ready framework for omics data to detect both individu...

High dimensionality omics and hyperspectral imaging datasets present difficult challenges for feature extraction and data mining due to huge numbers of features that cannot be simultaneously examined. The sample numbers and variables of these methods are constantly growing as new technologies are developed, and computational analysis needs to evolv...

Background Novel computational algorithms for multi-omics analysis bear great potential to highlight pathomechanisms of monogenic diseases. We recently defined the in-depth proteome of primary human neutrophil granulocytes (PMID 30630937). Here, we ask the question whether proteotypic patterns differ between defined genetic subtypes associated with...

Neutrophil granulocyte play pivotal roles in inflammatory responses, immune defence, tissue remodeling, and cancer control. Studying rare patients with defects in differentiation and/or function of neutrophil granulocytes highlights genes and pathways orchestrating these important cellular functions. A previously not appreciated role of the signal...

Assigning functions to the vast array of proteins present in eukaryotic cells remains challenging. To identify relationships between proteins, and thereby enable functional annotation of proteins, we determined changes in abundance of 10,323 human proteins in response to 294 biological perturbations using isotope-labeling mass spectrometry. We appl...

The annotation of protein function is a longstanding challenge of cell biology that suffers from the sheer magnitude of the task. Here we present ProteomeHD, which documents the response of 10,323 human proteins to 294 biological perturbations, measured by isotope-labelling mass spectrometry. Using this data matrix and robust machine learning we cr...

Gene co-expression analysis is a widespread method to identify the potential biological function of uncharacterised genes. Recent evidence suggests that proteome profiling may provide more accurate results than transcriptome profiling. However, it is unclear which statistical measure is best suited to detect proteins that are co-regulated. We have...

Neutrophil granulocytes are critical mediators of innate immunity and tissue regeneration. Rare diseases of neutrophil granulocytes may affect their differentiation and/or functions. However, there are very few validated diagnostic tests assessing the functions of neutrophil granulocytes in these diseases. Here, we set out to probe omics analysis a...

High-throughput methodologies and machine learning have been central in developing systems-level perspectives in molecular biology. Unfortunately, performing such integrative analyses has traditionally been reserved for bioinformaticians. This is now changing with the appearance of resources to help bench-side biologists become skilled at computati...

Background and objective Neutrophil granulocytes (NG) are critical mediators of innate immunity and tissue regeneration. Few monogenic diseases affecting their differentiation and/or function have been described, yet a systems-biology perspective has not yet been opened. We set out to define the proteome and transcriptome of NG from healthy individ...

Genes are often co-expressed with their genomic neighbors, even if these are functionally unrelated. For small expression changes driven by genetic variation within the same cell type, non-functional mRNA co-expression is not propagated to the protein level. However, it is unclear if protein levels are also buffered against any non-functional mRNA...

Genes are not randomly distributed in the genome. In humans, 10% of protein-coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. Here we show that coexpression of bidirectional gene pairs, and closeby gen...

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Supplementary Material

Subcellular localisation is an important aspect of protein function, but the protein composition of many intracellular compartments is poorly characterised. For example, many nuclear bodies are challenging to isolate biochemically and thus remain inaccessible to proteomics. Here we explore covariation in proteomics data as an alternative route to s...