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Metabolite and reaction inference based on enzyme specificities

De Groot, M.J.L. (author), Van Berlo, R.J.P. (author), Van Winden, W.A. (author), Verheijen, P.J.T. (author), Reinders, M.J.T. (author), De Ridder, D. (author)

Motivation: Many enzymes are not absolutely specific, or even promiscuous: they can catalyze transformations of more compounds than the traditional ones as listed in e.g. KEGG. This information is currently only available in databases, such as the BRENDA enzyme activity database. In this paper, we propose to model enzyme aspecificity by...

journal article 2009

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De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology

Nijkamp, J.F. (author), Van den Broek, M.A. (author), Datema, E. (author), De Kok, S. (author), Bosman, L. (author), Luttik, M.A.H. (author), Daran-Lapujade, P.A.S. (author), Vongsangnak, W. (author), Nielsen, J. (author), Heijne, W.H.M. (author), Klaassen, P. (author), Paddon, C.J. (author), Platt, D. (author), Kötter, P. (author), Van Ham, R.C. (author), Reinders, M.J.T. (author), Pronk, J.T. (author), De Ridder, D. (author), Daran, J.M. (author)

Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization compared to the reference strain S. cerevisiae...

journal article 2012

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Understanding Regulation of Metabolism through Feasibility Analysis

Nikerel, I.E. (author), Berkhout, J. (author), Hu, F. (author), Teusink, B. (author), Reinders, M.J.T. (author), De Ridder, D. (author)

Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but through non-obvious combinations of hierarchical ...

journal article 2012

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Exploring Sequence Characteristics Related to High- Level Production of Secreted Proteins in Aspergillus niger

Van den Berg, B.A. (author), Reinders, M.J.T. (author), Hulsman, M. (author), Wu, L. (author), Pel, H.J. (author), Roubos, J.A. (author), De Ridder, D. (author)

Protein sequence features are explored in relation to the production of over-expressed extracellular proteins by fungi. Knowledge on features influencing protein production and secretion could be employed to improve enzyme production levels in industrial bioprocesses via protein engineering. A large set, over 600 homologous and nearly 2,000...

journal article 2012

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Detecting recurrent gene mutation in interaction network context using multi-scale graph diffusion

Babaei, S. (author), Hulsman, M. (author), Reinders, M.J.T. (author), De Ridder, J. (author)

Background Delineating the molecular drivers of cancer, i.e. determining cancer genes and the pathways which they deregulate, is an important challenge in cancer research. In this study, we aim to identify pathways of frequently mutated genes by exploiting their network neighborhood encoded in the protein-protein interaction network. To this end...

journal article 2013

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Hypergeometric analysis of tiling-array and sequence data: Detection and interpretation of peaks

Taskesen, E. (author), Hoogeboezem, R. (author), Delwel, R. (author), Reinders, M.J.T. (author)

Probing protein-deoxyribonucleic acid (DNA) is gaining popularity as it sheds light on molecular mechanisms that regulate the expression of genes. Currently, tiling-arrays and next-generation sequencing technology can be used to measure these interactions. Both methods generate a signal over the genome in which contiguous regions of peaks on the...

journal article 2013

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SPiCE: A web-based tool for sequence-based protein classification and exploration

Van den Berg, B.A. (author), Reinders, M.J. (author), Roubos, J.A. (author), De Ridder, D. (author)

Background Amino acid sequences and features extracted from such sequences have been used to predict many protein properties, such as subcellular localization or solubility, using classifier algorithms. Although software tools are available for both feature extraction and classifier construction, their application is not straightforward,...

journal article 2014

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Integration of gene expression and DNA-methylation profiles improves molecular subtype classification in acute myeloid leukemia

Taskesen, E. (author), Babaei, S. (author), Reinders, M.J.M. (author), De Ridder, J. (author)

Background Acute Myeloid Leukemia (AML) is characterized by various cytogenetic and molecular abnormalities. Detection of these abnormalities is important in the risk-classification of patients but requires laborious experimentation. Various studies showed that gene expression profiles (GEP), and the gene signatures derived from GEP, can be used...

journal article 2015

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An integrated approach of gene expression and DNA-methylation profiles of WNT signaling genes uncovers novel prognostic markers in Acute Myeloid Leukemia

Taskesen, E. (author), Staal, F.J.T. (author), Reinders, M.J.T. (author)

Background The wingless-Int (WNT) pathway has an essential role in cell regulation of hematopoietic stem cells (HSC). For Acute Myeloid Leukemia (AML), the malignant counterpart of HSC, currently only a selective number of genes of the WNT pathway are analyzed by using either gene expression or DNA-methylation profiles for the identification of...

journal article 2015

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Insight into neutral and disease-associated human genetic variants through interpretable predictors

Van den Berg, B.A. (author), Reinders, M.J.T. (author), De Ridder, D. (author), De Beer, T.A.P. (author)

A variety of methods that predict human nonsynonymous single nucleotide polymorphisms (SNPs) to be neutral or disease-associated have been developed over the last decade. These methods are used for pinpointing disease-associated variants in the many variants obtained with next-generation sequencing technologies. The high performances of current...

journal article 2015

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Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

Babaei, S. (author), Mahfouz, A.M.E.T.A. (author), Hulsman, M. (author), Lelieveldt, B.P.F. (author), De Ridder, J. (author), Reinders, M.J.T. (author)

The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains...

journal article 2015

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Unbiased Quantitative Models of Protein Translation Derived from Ribosome Profiling Data

Gritsenko, A.A. (author), Hulsman, M. (author), Reinders, M.J.T. (author), De Ridder, D. (author)

Translation of RNA to protein is a core process for any living organism. While for some steps of this process the effect on protein production is understood, a holistic understanding of translation still remains elusive. In silico modelling is a promising approach for elucidating the process of protein synthesis. Although a number of...

journal article 2015

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Proteny: Discovering and visualizing statistically significant syntenic clusters at the proteome level

Gehrmann, T. (author), Reinders, M.J.T. (author)

Background: With more and more genomes being sequenced, detecting synteny between genomes becomes more and more important. However, for microorganisms the genomic divergence quickly becomes large, resulting in different codon usage and shuffling of gene order and gene elements such as exons. Results: We present Proteny, a methodology to detect...

journal article 2015

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Comparison of the indoor performance of 12 commercial PV products by a simple model

Apostolou, G. (author), Reinders, A.H.M.E. (author), Verwaal, M. (author)

This article presents a simple comparative model which has been developed for the estimation of the performance of photovoltaic (PV) products' cells in indoor environments. The model predicts the performance of PV solar cells, as a function of the distance from a spectrum of artificial (fluorescent light, halogen light, and light-emitting diodes...

journal article 2016

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2D Representation of Transcriptomes by t-SNE Exposes Relatedness between Human Tissues

Taskesen, E. (author), Reinders, M.J.T. (author)

The GTEx Consortium reported that hierarchical clustering of RNA profiles from 25 unique tissue types among 1641 individuals accurately distinguished the tissue types, but a multidimensional scaling failed to generate a 2D projection of the data that separates tissue-subtypes. In this study we show that a projection by t-Distributed Stochastic...

journal article 2016

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Pan-cancer subtyping in a 2D-map shows substructures that are driven by specific combinations of molecular characteristics

Taskesen, E. (author), Huisman, S.M.H. (author), Mahfouz, A.M.E.T.A. (author), Krijthe, J.H. (author), de Ridder, J. (author), van de Stolpe, A. (author), van den Akker, E.B. (author), Verhaegh, Wim (author), Reinders, M.J.T. (author)

The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to move from single genome-wide measurements in a...

journal article 2016

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Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease

Keo, D.L. (author), Aziz, N. Ahmad (author), Dzyubachyk, Oleh (author), Van Der Grond, Jeroen (author), van Roon-Mom, Willeke M.C. (author), Lelieveldt, B.P.F. (author), Reinders, M.J.T. (author), Mahfouz, A.M.E.T.A. (author)

Cytosine-adenine-guanine (CAG) repeat expansions in the coding regions of nine polyglutamine (polyQ) genes (HTT, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATN1, AR, and TBP) are the cause of several neurodegenerative diseases including Huntington’s disease (HD), six different spinocerebellar ataxias (SCAs), dentatorubral-pallidoluysian atrophy, and...

journal article 2017

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Predicting variant deleteriousness in non-human species: Applying the CADD approach in mouse

Groß, C. (author), de Ridder, D. (author), Reinders, M.J.T. (author)

Background: Predicting the deleteriousness of observed genomic variants has taken a step forward with the introduction of the Combined Annotation Dependent Depletion (CADD) approach, which trains a classifier on the wealth of available human genomic information. This raises the question whether it can be done with less data for non-human...

journal article 2018

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CHOP: Haplotype-aware path indexing in population graphs

Mokveld, T.O. (author), Linthorst, J. (author), Al-Ars, Z. (author), Holstege, H. (author), Reinders, M.J.T. (author)

The practical use of graph-based reference genomes depends on the ability to align reads to them. Performing substring queries to paths through these graphs lies at the core of this task. The combination of increasing pattern length and encoded variations inevitably leads to a combinatorial explosion of the search space. Instead of heuristic...

journal article 2020

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PCADD: SNV prioritisation in Sus scrofa

Groß, C. (author), Derks, Martijn (author), Megens, Hendrik Jan (author), Bosse, Mirte (author), Groenen, Martien A.M. (author), Reinders, M.J.T. (author), de Ridder, D. (author)

Background: In animal breeding, identification of causative genetic variants is of major importance and high economical value. Usually, the number of candidate variants exceeds the number of variants that can be validated. One way of prioritizing probable candidates is by evaluating their potential to have a deleterious effect, e.g. by...

journal article 2020