Michael Schubert's research while affiliated with EMBL-EBI and other places
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Publications (26)
Abstract Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community...
Aberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific expe...
Table S7. Associations between Drug Response and Molecular Data, Related to Figures 7 and S7
The predictive performance, data type and target pathway is shown for each association. The column “Corrected for ABCBs?” indicates whether the feature was predicted with the mean protein abundance of ABCB1 and ABCB11 regressed-out from drug response data.
Table S2. Relative Phosphopeptide Abundances in the COREAD Cell Lines, Related to Figures 6, S2, and S4
Scaled phosphopeptide quantification values for 50 colorectal cancer cell lines. Phosphopeptides are annotated by the known regulatory kinase and by KEGG pathway where applicable. The values are not corrected or normalized for total protein leve...
Enrichment of Gene Ontology, GSEA, KEGG, CORUM and Pfam terms for the WGCNA modules. Significance FDR is shown for each term.
Table S3. Correlation of Proteins belonging to Known CORUM Complexes, Related to Figure 1
Overlap of known CORUM protein complexes with the COREAD cell lines proteome. The mean and median correlation between protein complex components is shown for all complexes. Proteins with outlier profiles (high or low correlations) are labelled.
The entire WGCNA correlation network with weights greater than 0.02. The respective Pearson’s correlations are also shown and CORUM interactions are highlighted (value=1). Modules that are possibly driven by DNA copy number variations are highlighted (value=1).
Table S6. Proteomics and RNA-Seq Results for the ARID1A, ARID2, and PBRM1 CRISPR-cas9 Experiments, Related to Figure 4
Absolute and scaled S/N TMT values are shown for the proteomics data. ANOVA pvalues refer to any comparison between the WT, ARID1A, ARID2 and PBRM1 replicate groups. RNA-seq quantification and significance is shown only for the re...
Table S1. Relative Protein Abundances in the COREAD Cell Lines, Related to Figures 1, 2, 3, 5, 6, and 7
Scaled protein quantification values for 50 colorectal cancer cell lines. Proteins affected by mutations or DNA copy number alterations are annotated by ANOVA p value and average log2fold-changes where applicable.
Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of...
Assessing the extent to which genomic alterations compromise the integrity of the proteome is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labelling and tribrid mass spectrometry to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the relationships between g...
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy numbe...
Numerous pathway methods have been developed to quantify the signaling state of a cell from gene expression data, usually from the abundance of transcripts of pathway members, and are hence unable to take into account post-translational control of signal transduction. Gene expression signatures of pathway perturbations can capture this, but they ar...
BioModels (http://www.ebi.ac.uk/biomodels/) is a repository of mathematical models of biological processes. A large set of models is curated to verify both correspondence
to the biological process that the model seeks to represent, and reproducibility of the simulation results as described in
the corresponding peer-reviewed publication. Many models...
Horseradish peroxidases (HRPs) from Armoracia rusticana have long been utilized as reporters in various diagnostic assays and histochemical stainings. Regardless of their increasing importance in the field of life sciences and suggested uses in medical applications, chemical synthesis and other industrial applications, the HRP isoenzymes, their sub...
Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.
To increase the efficiency of model creation, the Path2Models project has automatically...
BioModels Database: curation and annotation
Citations
... To allow studying NEURON RxD models with other tools, we introduced neuron.rxd.export.sbml which allows exporting reaction dynamics at a point to SBML, a standard for representing systems biology models (Keating et al., 2020). ...
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... The psych and irr packages were used to calculate intraclass correlations. Pathway activity estimation from expression data was performed with PROGENy [43]. ...
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... Aneuploidy can lead to cellular stress through multiple pathways 5 . First, the imbalance of proteins arising from the change in chromosome copy number can lead to the increased presence of unfolded or misfolded proteins and consequently, proteotoxic stress 6,7 . In addition, there is evidence that aneuploid cells are under metabolic stress and have elevated levels of reactive oxygen species 1,8 . ...
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... For simplicity, we refer to the pipeline as described in 19 as the CARNIVAL pipeline. Briefly, PROGENy is used to infer pathway activity from the log2 FC of the infected immature enterocytes 2 gene expression data 87 . Next, using the TF-TGs interactions (from DoRothEA) and the differential expression data from infected organoids, VIPER was used to score TF activity based on enriched regulon analysis 88 . ...
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... In detail, the Illumina 450 k DNAm data from 48 purified immune-cells (6 × 8 cell-types) was derived from Reinius et al. [51]. From Iorio et al. [52] we obtained Illumina 450 k DNAm profiles for a total of 7 EAC cell-lines (ESO26, ESO51, FLO-1, KYAE-1, OACM5-1, OACP4C an SK-GT-4). For the squamous epithelial cells we first identified buccal swabs with over 95% purity, as determined with our HEpiDISH algorithm with the DNAm reference matrix defined above, and as applied to our large buccal swab 450 k DNAm dataset of 790 buccal swabs [32]. ...
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... The combinatorial properties occurring among the alterations are then analyzed and used to define cost functions, for example, based on the tendency of a group of genes to be mutated in a mutually exclusive manner. On the basis of these cost functions, optimal sub-networks are identified and interpreted as novel cancer driver pathways [22][23][24] . However, at the moment there is no consensual method to rigorously define a mathematical metric for mutual exclusivity and compute its statistical significance, and a number of interpretations exist 22,23,[25][26][27] . ...
... ac. uk/ biomo dels/ curat ion/ fbc) were combined in an OMEX archive file [49] deposited in BioModels [50] and assigned the identifier MODEL2201310001. ...
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... was synthesized and recombinantly expressed in E. coli. The isoenzyme C1A is the only isoenzyme with a solved structure, and Naatsaari et al. revised the sequence of HRP C1A in the database in 2014 [25]. Based on the traditional refolding method, HRP C1A was folded into an active form with native conformation and biological activity by a novel two-step dropwise dilution and an ultracentrifugation refolding strategy. ...
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... Along similar lines, a number of other pipelines fall into this category, including Path2Models [20], ModelSEED [21], PathwayTools [22], kBase [23], CarveMe [24], MetaDraft [25], and foundational protocols as detailed in [26], which are based on genome annotation, experimental literature evidences or biological databases. ...
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