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See detailMutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes
Schubert, Julian; Siekierska, Aleksandra; Langlois, Melanie UL et al

in Nature Genetics (2014), 46(12), 1327-32

Febrile seizures affect 2–4% of all children1 and have a strong genetic component2. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)3, 4, 5 have been identified that cause febrile ... [more ▼]

Febrile seizures affect 2–4% of all children1 and have a strong genetic component2. Recurrent mutations in three main genes (SCN1A, SCN1B and GABRG2)3, 4, 5 have been identified that cause febrile seizures with or without epilepsy. Here we report the identification of mutations in STX1B, encoding syntaxin-1B6, that are associated with both febrile seizures and epilepsy. Whole-exome sequencing in independent large pedigrees7, 8 identified cosegregating STX1B mutations predicted to cause an early truncation or an in-frame insertion or deletion. Three additional nonsense or missense mutations and a de novo microdeletion encompassing STX1B were then identified in 449 familial or sporadic cases. Video and local field potential analyses of zebrafish larvae with antisense knockdown of stx1b showed seizure-like behavior and epileptiform discharges that were highly sensitive to increased temperature. Wild-type human syntaxin-1B but not a mutated protein rescued the effects of stx1b knockdown in zebrafish. Our results thus implicate STX1B and the presynaptic release machinery in fever-associated epilepsy syndromes. [less ▲]

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See detailCommunity-integrated omics links dominance of a microbial generalist to fine-tuned resource usage
Muller, Emilie UL; Pinel, Nicolas; Laczny, Cedric Christian UL et al

in Nature Communications (2014)

Microbial communities are complex and dynamic systems that are primarily structured according to their members’ ecological niches. To investigate how niche breadth (generalist versus specialist lifestyle ... [more ▼]

Microbial communities are complex and dynamic systems that are primarily structured according to their members’ ecological niches. To investigate how niche breadth (generalist versus specialist lifestyle strategies) relates to ecological success, we develop and apply an integrative workflow for the multi-omic analysis of oleaginous mixed microbial communities from a biological wastewater treatment plant. Time- and space-resolved coupled metabolomic and taxonomic analyses demonstrate that the community-wide lipid accumulation phenotype is associated with the dominance of the generalist bacterium Candidatus Microthrix spp. By integrating population-level genomic reconstructions (reflecting fundamental niches) with transcriptomic and proteomic data (realised niches), we identify finely tuned gene expression governing resource usage by Candidatus Microthrix parvicella over time. Moreover, our results indicate that the fluctuating environmental conditions constrain the accumulation of genetic variation in Candidatus Microthrix parvicella likely due to fitness trade-offs. Based on our observations, niche breadth has to be considered as an important factor for understanding the evolutionary processes governing (microbial) population sizes and structures in situ. [less ▲]

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See detailMolecular and Clinical Evidence for an ARMC5 Tumor Syndrome: Concurrent Inactivating Germline and Somatic Mutations are Associated with both Primary Macronodular Adrenal Hyperplasia and Meningioma
Eibelt, Ulf; Trovato, Alissa; Kloth, Michael et al

in Journal of Clinical Endocrinology and Metabolism (2014)

Context:Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome (CS), which may present in the context of different familial multitumor syndromes. Heterozygous inactivating ... [more ▼]

Context:Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome (CS), which may present in the context of different familial multitumor syndromes. Heterozygous inactivating germline mutations of armadillo repeat containing 5 (ARMC5) have very recently been described as cause for sporadic PMAH. Whether this genetic condition also causes familial PMAH in association with other neoplasias is unclear. Objective: The aim of the present study was to delineate the molecular cause in a large family with PMAH and other neoplasias. Patients and Methods: Whole genome sequencing and comprehensive clinical and biochemical phenotyping was performed in members of a PMAH affected family. Nodules derived from adrenal surgery and pancreatic and meningeal tumor tissue were analysed for accompanying somatic mutations in the identified target genes. Results: PMAH presenting either as overt or subclinical CS was accompanied by a heterozygous germline mutation in ARMC5 (p.A110fs*9) located on chromosome 16. Analysis of tumor tissue showed different somatic ARMC5 mutations in adrenal nodules supporting a “second hit” hypothesis with inactivation of a tumor suppressor gene. A damaging somatic ARMC5 mutation was also found in a concomitant meningioma (p.R502fs) but not in a pancreatic tumor suggesting biallelic inactivation of ARMC5 as causal also for the intracranial meningioma. Conclusions: Our analysis further confirms inherited inactivating ARMC5 mutations as a cause of familial PMAH and suggests an additional role for the development of concomitant intracranial meningiomas. [less ▲]

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See detailDe Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies
Appenzeller, Silke; Balling, Rudi UL; Barisic, Nina et al

in American Journal of Human Genetics (2014), 4

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic ... [more ▼]

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the “classical” epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 × 10−4), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de novo mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction. [less ▲]

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See detailDe novo mutations in HCN1 cause early infantile epileptic encephalopathy
Nava, Caroline; Dalle, Carine; Rastetter, Agnès et al

in Nature Genetics (2014)

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See detailMercator: A fast and simple web server for genome scale functional annotation of plant sequence data
Lohse, Marc; Nagel, Axel; Herter, Thomas et al

in Plant, Cell and Environment (2014), 37(5), 1250-8

Next-generation technologies generate an overwhelming amount of gene sequence data. Efficient annotation tools are required, to make this data amenable to functional genomics analyses. The Mercator ... [more ▼]

Next-generation technologies generate an overwhelming amount of gene sequence data. Efficient annotation tools are required, to make this data amenable to functional genomics analyses. The Mercator pipeline automatically assigns functional terms to protein or nucleotide sequences. It uses the MapMan “BIN” ontology, which is tailored for functional annotation of plant “omics” data. The classification procedure performs parallel sequence searches against reference databases, compiles the results, and computes the most likely MapMan BINs for each query. In the current version, the pipeline relies on manually curated reference classifications originating from the three reference organisms (Arabidopsis, Chlamydomonas, rice), various other plant species that have a reviewed SwissProt annotation, and more than 2000 protein domain and family profiles at InterPro, CDD and KOG. Functional annotations predicted by Mercator achieve accuracies above 90% when benchmarked against manual annotation. In addition to mapping files for direct use in the visualization software MapMan, Mercator provides graphical overview charts, detailed annotation information in a convenient web browser interface and a MapMan-to-GO translation Table to export results as GO terms. Mercator is available free of charge via http://mapman.gabipd.org/web/guest/app/Mercator. [less ▲]

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See detailCommunity integrated omics links the dominance of a microbial generalist to fine-tuned resource usage
Muller, Emilie UL; Pinel, Nicolás; Laczny, Cedric Christian UL et al

Scientific Conference (2014)

Microbial communities are complex and dynamic systems that are influenced by stochastic-neutral processes but are mainly structured by resource availability and usage. High-resolution “meta-omics” offer ... [more ▼]

Microbial communities are complex and dynamic systems that are influenced by stochastic-neutral processes but are mainly structured by resource availability and usage. High-resolution “meta-omics” offer exciting prospects to investigate microbial populations in their native environment. In particular, integrated meta-omics, by allowing simultaneous resolution of fundamental niches (genomics) and realised niches (transcriptomics, proteomics and metabolomics), can resolve microbial lifestyles (generalist versus specialist lifestyle strategies) in situ. We have recently developed the necessary wet- and dry-lab methodologies to carry out systematic molecular measurements of microbial consortia over space and time, and to integrate and analyse the resulting data at the population-level. We applied these methods to oleaginous mixed microbial communities located on the surface of anoxic biological wastewater treatment tanks to investigate how niche breadth (generalist versus specialist lifestyle strategies) relates to community-level phenotypes and ecological success (i.e. population size). Coupled metabolomics and 16S rRNA gene-based deep sequencing demonstrate that the community-wide lipid accumulation phenotype is associated with the dominance of Candidatus Microthrix parvicella. By integrating population-level genomic reconstructions with transcriptomic and proteomic data, we found that the dominance of this microbial generalist population results from finely tuned resource usage and optimal foraging behaviour. Moreover, the fluctuating environmental conditions constrain the accumulation of variations, leading to a genetically homogeneous population likely due to fitness trade-offs. By integrating metagenomic, metatranscriptomic, metaproteomic and metabolomic information, we demonstrate that natural microbial population sizes and structures are intricately linked to resource usage and that differing microbial lifestyle strategies may explain the varying degrees of within-population genetic heterogeneity observed in metagenomic datasets. Elucidating the exact mechanism driving fitness trade-offs, e.g., antagonistic pleiotropy or others, will require additional integrated omic datasets to be generated from samples taken over space and time. Based on our observations, niche breadth and lifestyle strategies (generalists versus specialists) have to be considered as important factors for understanding the evolutionary processes governing microbial population sizes and structures in situ. [less ▲]

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See detailCommunity integrated omics links the dominance of a microbial generalist to fine-tuned resource usage
Muller, Emilie UL; Pinel, Nicolás; Laczny, Cedric Christian UL et al

Poster (2014)

Microbial communities are complex and dynamic systems that are influenced by stochastic-neutral processes but are mainly structured by resource availability and usage. High-resolution “meta-omics” offer ... [more ▼]

Microbial communities are complex and dynamic systems that are influenced by stochastic-neutral processes but are mainly structured by resource availability and usage. High-resolution “meta-omics” offer exciting prospects to investigate microbial populations in their native environment. In particular, integrated meta-omics, by allowing simultaneous resolution of fundamental niches (genomics) and realised niches (transcriptomics, proteomics and metabolomics), can resolve microbial lifestyles strategies (generalist versus specialist) in situ. We have recently developed the necessary wet- and dry-lab methodologies to carry out systematic molecular measurements of microbial consortia over space and time, and to integrate and analyse the resulting data at the population-level. We applied these methods to oleaginous mixed microbial communities located on the surface of anoxic biological wastewater treatment tanks to investigate how niche breadth (generalist versus specialist strategies) relates to community-level phenotypes and ecological success (i.e. population size). Coupled metabolomics and 16S rRNA gene-based deep sequencing demonstrate that the community-wide lipid accumulation phenotype is associated with the dominance of Candidatus Microthrix parvicella. By integrating population-level genomic reconstructions with transcriptomic and proteomic data, we found that the dominance of this microbial generalist population results from finely tuned resource usage and optimal foraging behaviour. Moreover, the fluctuating environmental conditions constrain the accumulation of variations, leading to a genetically homogeneous population likely due to fitness trade-offs. By integrating metagenomic, metatranscriptomic, metaproteomic and metabolomic information, we demonstrate that natural microbial population sizes and structures are intricately linked to resource usage and that differing microbial lifestyle strategies may explain the varying degrees of within-population genetic heterogeneity observed in metagenomic datasets. Elucidating the exact mechanism driving fitness trade-offs, e.g., antagonistic pleiotropy or others, will require additional integrated omic datasets to be generated from samples taken over space and time. Based on our observations, niche breadth and lifestyle strategies (generalists versus specialists) have to be considered as important factors for understanding the evolutionary processes governing microbial population sizes and structures in situ. [less ▲]

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See detailPOMO - Plotting Omics analysis results for Multiple Organisms
Lin, Jake UL; Kreisberg, Richard; Kallio, Aleksi et al

in BMC Genomics (2013), 14(918),

Background Systems biology experiments studying different topics and organisms produce thousands of data values across different types of genomic data. Further, data mining analyses are yielding ranked ... [more ▼]

Background Systems biology experiments studying different topics and organisms produce thousands of data values across different types of genomic data. Further, data mining analyses are yielding ranked and heterogeneous results and association networks distributed over the entire genome. The visualization of these results is often difficult and standalone web tools allowing for custom inputs and dynamic filtering are limited. Results We have developed POMO (http://pomo.cs.tut.fi), an interactive web-based application to visually explore omics data analysis results and associations in circular, network and grid views. The circular graph represents the chromosome lengths as perimeter segments, as a reference outer ring, such as cytoband for human. The inner arcs between nodes represent the uploaded network. Further, multiple annotation rings, for example depiction of gene copy number changes, can be uploaded as text files and represented as bar, histogram or heatmap rings. POMO has built-in references for human, mouse, nematode, fly,yeast, zebrafish, rice, tomato, Arabidopsis, and Escherichia coli. In addition, POMO provides custom options that allow integrated plotting of unsupported strains or closely related species associations, such as human and mouse orthologs or two yeast wild types, studied together within a single analysis. The web application also supports interactive label and weight filtering. Every iterative filtered result in POMO can be exported as image file and text file for sharing or direct future input. Conclusions The POMO web application is a unique tool for omics data analysis, which can be used to visualize and filter the genome-wide networks in the context of chromosomal locations as well as multiple network layouts. With the several illustration and filtering options the tool supports the analysis and visualization of any heterogeneous omics data analysis association results for many organisms. POMO is freely available and does not require any installation or registration. [less ▲]

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See detailGenomic Sequence Diversity and Population Structure of Saccharomyces cerevisiae Assessed by RAD-seq
Cromie, Gareth A.; Hyma, Katie E.; Ludlow, Catherine L. et al

in Genes, Genomes and Genomics (2013), 3(12), 2163-2171

The budding yeast Saccharomyces cerevisiae is important for human food production and as a model organism for biological research. The genetic diversity contained in the global population of yeast strains ... [more ▼]

The budding yeast Saccharomyces cerevisiae is important for human food production and as a model organism for biological research. The genetic diversity contained in the global population of yeast strains represents a valuable resource for a number of fields, including genetics, bioengineering, and studies of evolution and population structure. Here, we apply a multiplexed, reduced genome sequencing strategy (known as RAD-seq) to genotype a large collection of S. cerevisiae strains, isolated from a wide range of geographical locations and environmental niches. The method permits the sequencing of the same 1% of all genomes, producing a multiple sequence alignment of 116,880 bases across 262 strains. We find diversity among these strains is principally organized by geography, with European, North American, Asian and African/S. E. Asian populations defining the major axes of genetic variation. At a finer scale, small groups of strains from cacao, olives and sake are defined by unique variants not present in other strains. One population, containing strains from a variety of fermentations, exhibits high levels of heterozygosity and mixtures of alleles from European and Asian populations, indicating an admixed origin for this group. In the context of this global diversity, we demonstrate that a collection of seven strains commonly used in the laboratory encompasses only one quarter of the genetic diversity present in the full collection of strains, underscoring the relatively limited genetic diversity captured by the current set of lab strains. We propose a model of geographic differentiation followed by human-associated admixture, primarily between European and Asian populations and more recently between European and North American populations. The large collection of genotyped yeast strains characterized here will provide a useful resource for the broad community of yeast researchers. [less ▲]

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See detailThe Effects of Carbon Dioxide and Temperature on microRNA Expression in Arabidopsis Development
May, Patrick UL; Liao, Will; Wu, Yijin et al

in Nature Communications (2013), 4(2145),

Elevated levels of CO2 and temperature can both affect plant growth and development, but the molecular pathways and signaling mechanisms regulating these processes are still obscure. MicroRNAs function to ... [more ▼]

Elevated levels of CO2 and temperature can both affect plant growth and development, but the molecular pathways and signaling mechanisms regulating these processes are still obscure. MicroRNAs function to silence gene expression, and environmental stresses can alter their expressions to modulate plant phenotypes. Here we show, using the small RNA-sequencing method, the identification of microRNAs that are changed significantly in expression by either doubling the atmospheric CO2 concentration or by increasing temperature 3-6˚C. Notably, nearly all CO2-influenced microRNAs are also affected by elevated temperature. Using the RNA-sequencing method, we determine strongly correlated expression changes between miR156/157 and miR172 and their target transcription factors under elevated CO2 concentration, suggesting a mechanism for a CO2-induced early flowering phenotype. Similar correlations are also revealed for microRNAs acting in auxin-signaling, stress responses, and potential cell wall carbohydrate synthesis. Our results demonstrate that elevated CO2 and elevated temperature can signal microRNA expressions to affect Arabidopsis growth and development, and microRNA regulation of flowering time might underlie the onset of flowering affected by increasing CO2. [less ▲]

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See detailHigh-throughput tetrad analysis
Ludlow, Catherine L.; Scott, Adrian C.; Cromie, Gareth A. et al

in Nature Methods (2013), 10

Tetrad analysis has been a gold-standard genetic technique for several decades. Unfortunately, the need to manually isolate, disrupt and space tetrads has relegated its application to small-scale studies ... [more ▼]

Tetrad analysis has been a gold-standard genetic technique for several decades. Unfortunately, the need to manually isolate, disrupt and space tetrads has relegated its application to small-scale studies and limited its integration with high-throughput DNA sequencing technologies. We have developed a rapid, high-throughput method, called barcode-enabled sequencing of tetrads (BEST), that uses (i) a meiosis-specific GFP fusion protein to isolate tetrads by FACS and (ii) molecular barcodes that are read during genotyping to identify spores derived from the same tetrad. Maintaining tetrad information allows accurate inference of missing genetic markers and full genotypes of missing (and presumably nonviable) individuals. An individual researcher was able to isolate over 3,000 yeast tetrads in 3 h, an output equivalent to that of almost 1 month of manual dissection. BEST is transferable to other microorganisms for which meiotic mapping is significantly more laborious. [less ▲]

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See detailSystematic molecular measurements reveal key microbial populations driving community-wide phenotype
Muller, Emilie UL; Pinel, Nicolás; May, Patrick UL et al

Poster (2013)

Natural microbial communities are heterogeneous and dynamic. Therefore, a major consideration for multiple omic data studies is the sample-to-sample heterogeneity, which can lead to inconsistent results ... [more ▼]

Natural microbial communities are heterogeneous and dynamic. Therefore, a major consideration for multiple omic data studies is the sample-to-sample heterogeneity, which can lead to inconsistent results if the different biomolecular fractions are obtained from distinct sub-samples. Conversely, systematic omic measurements, i.e. the standardised, reproducible and simultaneous measurement of multiple features from a single undivided sample, result in fully integrable datasets. Objective In order to prove the feasibility and benefits of such systematic measurements in the study of the respective contributions of different populations to the community-wide phenotype, we purified and analysed all biomolecular fractions, i.e. DNA, RNA, proteins and metabolites, obtained from a unique undivided sample of lipid accumulating microbial community (LAMC) from wastewater treatment plant and integrate the resulting datasets. Methods One time point of particular interest was first selected out of 4 LAMC samples for its high diversity and strong lipid accumulation phenotype. Then, the systematic measurement strategy was applied to the selected undivided LAMC sample and the purified biomolecules were analysed by high-throughput techniques. DNA and RNA sequencing reads were assembled at the population-level using different binning strategies. A database, containing predicted proteins, was constructed to identify the detected peptides. Finally, all biomolecular information was mapped onto the assembled composite genomes to identify the precise roles of the different populations in the community-wide lipid accumulation phenotype. Results Metabolomics and 16S diversity analyses were used to select the sample of highest interest for detailed analysis. The systematic measurements of the selected sample followed by data integration have allowed us to probe the functional relevance of the population-level composite genomes, leading to the identification of the LAMC key players. Conclusion As community phenotype is not the sum of the different partner phenotypes, understanding a microbial community system requires more than the study of isolated organisms. Even if both approaches are complementary, top-down systematic approached only provides a holistic perspective of micro-ecological processes. [less ▲]

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See detailA model microbial community for Eco-Systems Biology
Muller, Emilie UL; Roume, Hugo UL; Buschart, Anna UL et al

Poster (2013)

Objective Microbial communities (MCs) play crucial roles in human health and disease. In-depth characterization of the vast organismal and functional diversity of MCs is now facilitated by high-resolution ... [more ▼]

Objective Microbial communities (MCs) play crucial roles in human health and disease. In-depth characterization of the vast organismal and functional diversity of MCs is now facilitated by high-resolution molecular approaches. Systematic measurements are key for meaningful data integration, analysis and modeling. Based on a model MC from a biological wastewater treatment plant, we have developed a new framework based on wet- and dry-lab methods for the integrated analyses of MCs at the population- as well as at the community-level. Methods The overall methodological framework first relies on a standardised wet-lab procedure for the isolation of concomitant biomolecules, i.e., DNA, RNA, proteins and metabolites, from single undivided samples. Purified biomolecular fractions then are subjected to high-resolution omic analyses including metagenomics, metatranscriptomics, metaproteomics and (meta-) metabolomics. The resulting data form the input for integrated bioinformatic analyses. Population-level integrated omic analyses rely on a newly developed binning and re-assembly method, which yields near-complete genome reconstructions for dominant populations. Community-level analyses involve the reconstruction of community-wide metabolic networks. Functional omic data is then mapped onto these reconstructions and contextualized. Results Application of the population-centric workflow has allowed us to reconstruct and identify 10 major populations within the model MC and has led to the identification of a key generalist population, Candidatus Microthrix spp., within the community. Analysis of the community-wide metabolic networks has allowed the identification of keystone genes involved in lipid and nitrogen metabolism within the MC. Conclusions Our new methodological framework offers exciting new prospects for elucidating the functional relevance of specific populations and genes within MCs. The established workflows are now being applied to samples of biomedical research interest such as human gastrointestinal tract-derived samples. [less ▲]

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See detailA Protein Prioritization Approach Tailored for the FA/BRCA Pathway
Haitjema, Anneke; Brandt, Bernd W.; Ameziane, Najim et al

in PLoS ONE (2013), 8(4), 62017

<sec><title/><p>Fanconi anemia (FA) is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which ... [more ▼]

<sec><title/><p>Fanconi anemia (FA) is a heterogeneous recessive disorder associated with a markedly elevated risk to develop cancer. To date sixteen FA genes have been identified, three of which predispose heterozygous mutation carriers to breast cancer. The FA proteins work together in a genome maintenance pathway, the so-called FA/BRCA pathway which is important during the <italic>S</italic> phase of the cell cycle. Since not all FA patients can be linked to (one of) the sixteen known complementation groups, new FA genes remain to be identified. In addition the complex FA network remains to be further unravelled. One of the FA genes, <italic>FANCI</italic>, has been identified via a combination of bioinformatic techniques exploiting FA protein properties and genetic linkage. The aim of this study was to develop a prioritization approach for proteins of the entire human proteome that potentially interact with the FA/BRCA pathway or are novel candidate FA genes. To this end, we combined the original bioinformatics approach based on the properties of the first thirteen FA proteins identified with publicly available tools for protein-protein interactions, literature mining (Nermal) and a protein function prediction tool (FuncNet). Importantly, the three newest FA proteins FANCO/RAD51C, FANCP/SLX4, and XRCC2 displayed scores in the range of the already known FA proteins. Likewise, a prime candidate FA gene based on next generation sequencing and having a very low score was subsequently disproven by functional studies for the FA phenotype. Furthermore, the approach strongly enriches for GO terms such as DNA repair, response to DNA damage stimulus, and cell cycle-regulated genes. Additionally, overlaying the top 150 with a haploinsufficiency probability score, renders the approach more tailored for identifying breast cancer related genes. This approach may be useful for prioritization of putative novel FA or breast cancer genes from next generation sequencing efforts.</p></sec> [less ▲]

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