Martijn Huynen

Martijn Huynen
Radboud University Medical Centre (Radboudumc) · Centre for Molecular and Biomolecular Informatics

About

508
Publications
59,843
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24,659
Citations

Publications

Publications (508)
Article
Full-text available
The cervicovaginal microbiome (CVM) correlates with women’s cervical health, and variations in its composition are associated with high-risk human papillomavirus (hrHPV) infection outcomes. Cervicovaginal microbes have been grouped into five community state types (CSTs) based on microbial community composition and abundance. However, studying the i...
Article
Full-text available
Cervical cancer is the third leading cause of female cancers globally, resulting in more than 300,000 deaths every year. The majority of all cervical cancers are caused by persistent infections with high-risk human papillomaviruses (hrHPV) that can progress to cancer via a series of premalignant lesions. Most women, however, clear this infection wi...
Article
Full-text available
Background Microbial pan-genomes are shaped by a complex combination of stochastic and deterministic forces. Even closely related genomes exhibit extensive variation in their gene content. Understanding what drives this variation requires exploring the interactions of gene products with each other and with the organism’s external environment. Howev...
Article
Full-text available
The mitochondrial respiratory chain (MRC) is composed of four multiheteromeric enzyme complexes. According to the endosymbiotic origin of mitochondria, eukaryotic MRC derives from ancestral proteobacterial respiratory structures consisting of a minimal set of complexes formed by a few subunits associated with redox prosthetic groups. These enzymes,...
Article
Full-text available
Background Because most cervical cancers are caused by high-risk human papillomaviruses (hrHPVs), cervical cancer prevention programs increasingly employ hrHPV testing as a primary test. The high sensitivity of HPV tests is accompanied by low specificity, resulting in high rates of overdiagnosis and overtreatment. Targeted circular probe-based RNA...
Article
Variation in complex composition provides clues about the function of individual subunits.
Article
Full-text available
Acellular pertussis (aP) booster vaccines are central to pertussis immunization programs, although their effectiveness varies. The Bacille Calmette-Guérin (BCG) vaccine is a prototype inducer of trained immunity, which enhances immune responses to subsequent infections or vaccinations. While previous clinical studies have demonstrated that trained...
Article
Full-text available
SUPV3L1 encodes a helicase that is mainly localised in the mitochondria. It has been shown in vitro to possess both double-stranded RNA and DNA unwinding activity that is ATP-dependent. Here we report the first two patients for this gene who presented with a homozygous preliminary stop codon in the C-terminus of SUPV3L1. They presented with a chara...
Article
Full-text available
Background The cervicovaginal microbiome (CVM) plays a significant role in women’s cervical health and disease. Microbial alterations at the species level and characteristic community state types (CST) have been associated with acquisition and persistence of high-risk human papillomavirus (hrHPV) infections that may result in progression of cervica...
Article
Full-text available
Although serological studies have shown that antibodies against SARS-CoV-2 play an important role in protection against (re)infection, the dynamics of mucosal antibodies during primary infection and their potential impact on viral load and the resolution of disease symptoms remain unclear. During the first pandemic wave, we assessed the longitudina...
Article
Full-text available
The unique biology and medical relevance of the mitochondrion of the malaria parasite Plasmodium falciparum
Article
Full-text available
Malaria parasite transmission to mosquitoes relies on the uptake of sexual stage parasites during a blood meal and subsequent formation of oocysts on the mosquito midgut wall. Transmission-blocking vaccines (TBVs) and monoclonal antibodies (mAbs) target sexual stage antigens to interrupt human-to-mosquito transmission and may form important tools f...
Article
The number of de novo mutations (DNMs) in the human germline is correlated with parental age at conception, but this explains only part of the observed variation. We investigated whether there is a family-specific contribution to the number of DNMs in offspring. The analysis of DNMs in 111 dizygotic twin pairs did not identify a substantial family-...
Article
Full-text available
Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes a...
Article
Full-text available
Plasmodium species, the causative agent of malaria, have a complex life cycle involving two hosts. The sporozoite life stage is characterized by an extended phase in the mosquito salivary glands followed by free movement and rapid invasion of hepatocytes in the human host. This transmission stage has been the subject of many transcriptomics and pro...
Article
Full-text available
Cefotaxime (CTX) is a third-generation cephalosporin (3GC) commonly used to treat infections caused by Escherichia coli . Two genetic mechanisms have been associated with 3GC resistance in E. coli . The first is the conjugative transfer of a plasmid harbouring antibiotic-resistance genes. The second is the introduction of mutations in the promoter...
Article
Full-text available
The majority of cellular energy is produced by the mitochondrial oxidative phosphorylation (OXPHOS) system. Failure of the first OXPHOS enzyme complex, NADH:ubiquinone oxidoreductase or complex I (CI), is associated with multiple signs and symptoms presenting at variable ages of onset. There is no approved drug treatment yet to slow or reverse the...
Article
Full-text available
Complexome profiling is an emerging 'omics' approach that systematically interrogates the composition of protein complexes (the complexome) of a sample, by combining biochemical separation of native protein complexes with mass-spectrometry based quantitation proteomics. The resulting fractionation profiles hold comprehensive information on the abun...
Preprint
Full-text available
Mucosal antibodies play a key role in protection against SARS-CoV-2 exposure, but their role during primary infection is not well understood. We assessed mucosal antibody responses during primary infection with SARS-CoV-2 and examined their relationship with viral load and clinical symptoms. Elevated mucosal IgM was associated with lower viral load...
Preprint
Full-text available
Plasmodium species have a single mitochondrion that is essential for their survival and has been successfully targeted by anti-malarial drugs. Most proteins are imported into this organelle and our picture of the Plasmodium mitochondrial proteome remains incomplete. Many data sources contain information about mitochondrial localization, including p...
Preprint
Full-text available
Microbial pan-genomes are shaped by a complex combination of stochastic and deterministic forces. Even closely related genomes often exhibit extensive variation in their gene content. Understanding what drives this variation requires exploring the interactions of genes with each other and with their external environments. However, to date, conceptu...
Preprint
Full-text available
Complexome profiling is an emerging 'omics approach that systematically interrogates the composition of protein complexes (the complexome) of a sample, by combining biochemical separation of native protein complexes with mass-spectrometry based quantitation proteomics. The resulting fractionation profiles hold comprehensive information on the abund...
Preprint
Full-text available
Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes a...
Preprint
Full-text available
The number of de novo mutations (DNMs) in the human germline is correlated with parental age at conception, but this explains only part of the observed variation. We investigated whether there is a family-specific contribution to the number of DNMs in offspring. The analysis of DNMs in 111 dizygotic twin pairs did not identify a significant family-...
Preprint
Full-text available
Plasmodium species, the causative agent of malaria, have a complex life cycle involving two hosts. The sporozoite life stage is characterized by an extended phase in the mosquito salivary glands followed by free movement and rapid invasion of hepatocytes in the human host. This transmission stage has been the subject of many transcriptomics and pro...
Preprint
Full-text available
Cefotaxime (CTX) is a commonly used third-generation cephalosporin (3GC) to treat infections caused by Escherichia coli . Two genetic mechanisms have been associated with 3GC resistance in E. coli . The first is the conjugative transfer of a plasmid harboring antibiotic resistance genes. The second is the introduction of mutations in the promoter r...
Article
Full-text available
Protein complexes from the oxidative phosphorylation (OXPHOS) system are assembled with the help of proteins called assembly factors. We here delineate the function of the inner mitochondrial membrane protein TMEM70, in which mutations have been linked to OXPHOS deficiencies, using a combination of BioID, complexome profiling and coevolution analys...
Article
Full-text available
We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections at a Dutch neonatal intensive care unit. Weekly neonatal MSSA carriage surveillance and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. Traditional clustering of MSSA isolates by spa typing and Multiple-Locus Vari...
Article
Full-text available
Background: Colorectal cancer (CRC) is a complex multifactorial disease. Increasing evidence suggests that the microbiome is involved in different stages of CRC initiation and progression. Beyond specific pro-oncogenic mechanisms found in pathogens, metagenomic studies indicate the existence of a microbiome signature, where particular bacterial ta...
Article
Full-text available
Many biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer. Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals. Identifying actionable hyperactive biological pathways in individual cancers may i...
Article
Full-text available
In order to synthesize the 13 oxidative phosphorylation proteins encoded by mammalian mtDNA, a large assortment of nuclear encoded proteins is required. These include mitoribosomal proteins and various RNA processing, modification and degradation enzymes. RNA crosslinking has been successfully applied to identify whole-cell poly(A) RNA-binding prot...
Article
Nearly all cervical cancers are initiated by a persistent infection with one of the high-risk human papillomaviruses (high-risk HPV). High-risk HPV DNA testing is highly sensitive but cannot distinguish between active, productive infections and dormant infections or merely deposited virus. A solution for this shortcoming may be the detection of tra...
Article
Full-text available
Motivation: Complexome profiling combines native gel electrophoresis with mass spectrometry to obtain the inventory, composition and abundance of multiprotein assemblies in an organelle. Applying complexome profiling to determine the effect of a mutation on protein complexes requires separating technical and biological variations from the variatio...
Preprint
Full-text available
Protein complexes from the oxidative phosphorylation (OXPHOS) system are assembled with the help of proteins called assembly factors. We here delineate the function of the inner mitochondrial membrane protein TMEM70, in which mutations have been linked to OXPHOS deficiencies, using a combination of BioID, complexome profiling and coevolution analys...
Article
Full-text available
The cilium is an essential organelle at the surface of mammalian cells whose dysfunction causes a wide range of genetic diseases collectively called ciliopathies. The current rate at which new ciliopathy genes are identified suggests that many ciliary components remain undiscovered. We generated and rigorously analyzed genomic, proteomic, transcrip...
Preprint
Full-text available
Background We observed an increase in methicillin-susceptible Staphylococcus aureus (MSSA) infections among neonates at a Dutch third level neonatal intensive care unit. Weekly surveillance data of MSSA carriage among neonates and cross-sectional screenings of health care workers (HCWs) were available for outbreak tracing. While traditional typing...
Article
Full-text available
Clear cell renal cell carcinoma (ccRCC) comprises more than 80% of all renal cancers and when metastasized leads to a 5-year survival rate of only 10%. The high rate of therapy failure and resistance development calls for reliable methods that provide information on the actionable biological pathways and predict optimal treatment protocols for indi...
Data
Transcripts for smMIP design. SmMIPs were designed against the antisense strand of predicted transcripts (UCSC human genome assembly hg19 and splice variant specific FASTA sequences). The genes listed are newly added to the panel published in de Bitter et al. (16).
Data
Gene expression in cluster a vs. cluster b (non-significant). Fold changes of cluster b/cluster a are indicated. Significance was determined using a Wilcoxon Mann-Whitney U-test with Benjamini Hochberg correction for multiple testing (p < 0.05, FDR < 0.01). Note that for significance, the p-value must not exceed the FDR. Significant differential ge...
Data
Mean FPM values for cell lines E98, SKRC7, and SKRC17.
Article
Full-text available
Background Genomic imprinting, resulting in parent-of-origin specific gene expression, plays a critical role in mammalian development. Here, we apply allele-specific RNA-seq on isogenic B6D2F1 mice to assay imprinted genes in tissues from early embryonic tissues between E3.5 and E7.25 and in pluripotent cell lines to evaluate maintenance of imprint...
Preprint
Full-text available
Lateral gene transfer (also known as Horizontal Gene Transfer) is the transmission of genetic material between phylogenetically unrelated organisms. Previous studies have been showing the importance of this process for the evolution of unicellular eukaryotes, particularly those living in highly competitive niches such as the herbivore gut. Pyromice...
Article
Full-text available
PIWI-interacting RNAs (piRNAs) comprise a class of small RNAs best known for suppressing transposable elements in germline tissues. The vector mosquito Aedes aegypti encodes seven PIWI genes, four of which are somatically expressed. This somatic piRNA pathway generates piRNAs from viral RNA during infection with cytoplasmic RNA viruses through ping...
Article
Full-text available
Cabeza ( caz ) is the single Drosophila melanogaster orthologue of the human FET proteins FUS, TAF15, and EWSR1, which have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. In this study, we identified Xrp1 , a nuclear chromatin-binding protein, as a key modifier of caz mutant phenotypes. Xrp1 expression was stron...
Preprint
Full-text available
Hundreds of biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer. Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals, leading to futile overtreatment. To acquire a comprehensive insight in aber...
Article
Full-text available
Most eukaryotic cells contain mitochondria with a genome that evolved from their α-proteobacterial ancestor. In the course of eukaryotic evolution, the mitochondrial genome underwent a dramatic reduction in size, caused by the loss and translocation of genes. This required adjustments in mitochondrial gene expression mechanisms and resulted in a co...
Article
All present‐day mitochondria originate from a single endosymbiotic event that gave rise to the last eukaryotic common ancestor (LECA) more than a billion years ago. However, to date, many aspects of mitochondrial evolution have remained unresolved. Comparative genomics and proteomics have revealed a complex evolutionary origin of many mitochondrial...
Preprint
Full-text available
Motivation: Complexome profiling combines native gel electrophoresis with mass spectrometry to obtain the inventory, composition and abundance of multiprotein assemblies in an organelle. Applying complexome profiling to determine the effect of a mutation on protein complexes requires separating technical and biological variations from the variation...
Preprint
Full-text available
TUDOR-domain containing proteins facilitate PIWI interacting (pi)RNA biogenesis in Drosophila melanogaster and other model organisms. In Aedes aegypti mosquitoes, a somatically active piRNA pathway generates piRNAs from viral RNA during acute infection with cytoplasmic RNA viruses. Viral piRNA biogenesis requires ping-pong amplification by the PIWI...
Article
Background: Whole genome sequencing (WGS) is rarely used for drug-resistance testing of Mycobacterium tuberculosis in high-endemic settings. We present the first study from Indonesia, which has the second highest tuberculosis (TB) burden worldwide, with less than 50% of drug-resistant cases currently detected. Methods: We applied WGS in strains...