Publications by authors named "Ivo Grosse"

93 Publications

Taxonomic analysis of metagenomic data with kASA.

Nucleic Acids Res 2021 Mar 30. Epub 2021 Mar 30.

Institute of Computer Science, Martin-Luther University Halle-Wittenberg, Von-Seckendorff-Platz 1, Halle, Germany.

The taxonomic analysis of sequencing data has become important in many areas of life sciences. However, currently available tools for that purpose either consume large amounts of RAM or yield insufficient quality and robustness. Here, we present kASA, a k-mer based tool capable of identifying and profiling metagenomic DNA or protein sequences with high computational efficiency and a user-definable memory footprint. We ensure both high sensitivity and precision by using an amino acid-like encoding of k-mers together with a range of multiple k's. Custom algorithms and data structures optimized for external memory storage enable a full-scale taxonomic analysis without compromise on laptop, desktop, and HPCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkab200DOI Listing
March 2021

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma.

Int J Mol Sci 2020 Aug 24;21(17). Epub 2020 Aug 24.

Institut für Medizinische Immunologie, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Str. 14, 06112 Halle (Saale), Germany.

Oral squamous cell carcinoma (OSCC) is the 10th most frequent human malignancy and is thus a global burden. Despite some progress in diagnosis and therapy, patients' overall survival rate, between 40 and 55%, has stagnated over the last four decades. Since the tumor node metastasis (TNM) system is not precise enough to predict the disease outcome, additive factors for diagnosis, prognosis, prediction and therapy resistance are urgently needed for OSCC. One promising candidate is the hypoxia inducible factor-1 (HIF-1), which functions as an early regulator of tumor aggressiveness and is a key promoter of energy adaptation. Other parameters comprise the composition of the tumor microenvironment, which determines the availability of nutrients and oxygen. In our opinion, these general processes are linked in the pathogenesis of OSCC. Based on this assumption, the review will summarize the major features of the HIF system-induced activities, its target proteins and related pathways of nutrient utilization and metabolism that are essential for the initiation, progression and therapeutic stratification of OSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21176083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504563PMC
August 2020

Insights gained from a comprehensive all-against-all transcription factor binding motif benchmarking study.

Genome Biol 2020 05 11;21(1):114. Epub 2020 May 11.

School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland.

Background: Positional weight matrix (PWM) is a de facto standard model to describe transcription factor (TF) DNA binding specificities. PWMs inferred from in vivo or in vitro data are stored in many databases and used in a plethora of biological applications. This calls for comprehensive benchmarking of public PWM models with large experimental reference sets.

Results: Here we report results from all-against-all benchmarking of PWM models for DNA binding sites of human TFs on a large compilation of in vitro (HT-SELEX, PBM) and in vivo (ChIP-seq) binding data. We observe that the best performing PWM for a given TF often belongs to another TF, usually from the same family. Occasionally, binding specificity is correlated with the structural class of the DNA binding domain, indicated by good cross-family performance measures. Benchmarking-based selection of family-representative motifs is more effective than motif clustering-based approaches. Overall, there is good agreement between in vitro and in vivo performance measures. However, for some in vivo experiments, the best performing PWM is assigned to an unrelated TF, indicating a binding mode involving protein-protein cooperativity.

Conclusions: In an all-against-all setting, we compute more than 18 million performance measure values for different PWM-experiment combinations and offer these results as a public resource to the research community. The benchmarking protocols are provided via a web interface and as docker images. The methods and results from this study may help others make better use of public TF specificity models, as well as public TF binding data sets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-020-01996-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212583PMC
May 2020

Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups.

Genes (Basel) 2020 04 17;11(4). Epub 2020 Apr 17.

Institute of Cytology and Genetics Siberian Branch of the Russian Academy of Sciences (SB RAS), 630090 Novosibirsk, Russia.

Gene expression profiling data contains more information than is routinely extracted with standard approaches. Here we present Fold-Change-Specific Enrichment Analysis (FSEA), a new method for functional annotation of differentially expressed genes from transcriptome data with respect to their fold changes. FSEA identifies Gene Ontology (GO) terms, which are shared by the group of genes with a similar magnitude of response, and assesses these changes. GO terms found by FSEA are fold-change-specifically (e.g., weakly, moderately, or strongly) affected by a stimulus under investigation. We demonstrate that many responses to abiotic factors, mutations, treatments, and diseases occur in a fold-change-specific manner. FSEA analyses suggest that there are two prevailing responses of functionally-related gene groups, either weak or strong. Notably, some of the fold-change-specific GO terms are invisible by classical algorithms for functional gene enrichment, Singular Enrichment Analysis (SEA), and Gene Set Enrichment Analysis (GSEA). These are GO terms not enriched compared to the genome background but strictly regulated by a factor within specific fold-change intervals. FSEA analysis of a cancer-related transcriptome suggested that the gene groups with a tightly coordinated response can be the valuable source to search for possible regulators, markers, and therapeutic targets in oncogenic processes. Availability and Implementation: FSEA is implemented as the FoldGO Bioconductor R package and a web-server.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes11040434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230499PMC
April 2020

Performance of Mapping Approaches for Whole-Genome Bisulfite Sequencing Data in Crop Plants.

Front Plant Sci 2020 28;11:176. Epub 2020 Feb 28.

Institute of Computer Science, Bioinformatics, Martin Luther University Halle-Wittenberg, Von Seckendorff-Platz 1, Halle (Saale), Germany.

DNA methylation is involved in many different biological processes in the development and well-being of crop plants such as transposon activation, heterosis, environment-dependent transcriptome plasticity, aging, and many diseases. Whole-genome bisulfite sequencing is an excellent technology for detecting and quantifying DNA methylation patterns in a wide variety of species, but optimized data analysis pipelines exist only for a small number of species and are missing for many important crop plants. This is especially important as most existing benchmark studies have been performed on mammals with hardly any repetitive elements and without CHG and CHH methylation. Pipelines for the analysis of whole-genome bisulfite sequencing data usually consists of four steps: read trimming, read mapping, quantification of methylation levels, and prediction of differentially methylated regions (DMRs). Here we focus on read mapping, which is challenging because un-methylated cytosines are transformed to uracil during bisulfite treatment and to thymine during the subsequent polymerase chain reaction, and read mappers must be capable of dealing with this cytosine/thymine polymorphism. Several read mappers have been developed over the last years, with different strengths and weaknesses, but their performances have not been critically evaluated. Here, we compare eight read mappers: Bismark, BismarkBwt2, BSMAP, BS-Seeker2, Bwameth, GEM3, Segemehl, and GSNAP to assess the impact of the read-mapping results on the prediction of DMRs. We used simulated data generated from the genomes of , , , , and , monitored the effects of the bisulfite conversion rate, the sequencing error rate, the maximum number of allowed mismatches, as well as the genome structure and size, and calculated precision, number of uniquely mapped reads, distribution of the mapped reads, run time, and memory consumption as features for benchmarking the eight read mappers mentioned above. Furthermore, we validated our findings using real-world data of and showed the influence of the mapping step on DMR calling in WGBS pipelines. We found that the conversion rate had only a minor impact on the mapping quality and the number of uniquely mapped reads, whereas the error rate and the maximum number of allowed mismatches had a strong impact and leads to differences of the performance of the eight read mappers. In conclusion, we recommend BSMAP which needs the shortest run time and yields the highest precision, and Bismark which requires the smallest amount of memory and yields precision and high numbers of uniquely mapped reads.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2020.00176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093021PMC
February 2020

Selective egg cell polyspermy bypasses the triploid block.

Elife 2020 02 6;9. Epub 2020 Feb 6.

Centre for Biomolecular Interactions, University of Bremen, Bremen, Germany.

Polyploidization, the increase in genome copies, is considered a major driving force for speciation. We have recently provided the first direct in planta evidence for polyspermy induced polyploidization. Capitalizing on a novel -based polyspermy assay, we here show that polyspermy can selectively polyploidize the egg cell, while rendering the genome size of the ploidy-sensitive central cell unaffected. This unprecedented result indicates that polyspermy can bypass the triploid block, which is an established postzygotic polyploidization barrier. In fact, we here show that most polyspermy-derived seeds are insensitive to the triploid block suppressor . The robustness of polyspermy-derived plants is evidenced by the first transcript profiling of triparental plants and our observation that these idiosyncratic organisms segregate tetraploid offspring within a single generation. Polyspermy-derived triparental plants are thus comparable to triploids recovered from interploidy crosses. Our results expand current polyploidization concepts and have important implications for plant breeding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.52976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004562PMC
February 2020

Urban areas as hotspots for bees and pollination but not a panacea for all insects.

Nat Commun 2020 Jan 29;11(1):576. Epub 2020 Jan 29.

General Zoology, Institute for Biology, Martin Luther University Halle-Wittenberg, Hoher Weg 8, 06120, Halle, Germany.

Urbanisation is an important global driver of biodiversity change, negatively impacting some species groups whilst providing opportunities for others. Yet its impact on ecosystem services is poorly investigated. Here, using a replicated experimental design, we test how Central European cities impact flying insects and the ecosystem service of pollination. City sites have lower insect species richness, particularly of Diptera and Lepidoptera, than neighbouring rural sites. In contrast, Hymenoptera, especially bees, show higher species richness and flower visitation rates in cities, where our experimentally derived measure of pollination is correspondingly higher. As well as revealing facets of biodiversity (e.g. phylogenetic diversity) that correlate well with pollination, we also find that ecotones in insect-friendly green cover surrounding both urban and rural sites boost pollination. Appropriately managed cities could enhance the conservation of Hymenoptera and thereby act as hotspots for pollination services that bees provide to wild flowers and crops grown in urban settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-14496-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989530PMC
January 2020

A single ChIP-seq dataset is sufficient for comprehensive analysis of motifs co-occurrence with MCOT package.

Nucleic Acids Res 2019 12;47(21):e139

Department of Natural Science, Novosibirsk State University, Novosibirsk 630090, Russia.

Recognition of composite elements consisting of two transcription factor binding sites gets behind the studies of tissue-, stage- and condition-specific transcription. Genome-wide data on transcription factor binding generated with ChIP-seq method facilitate an identification of composite elements, but the existing bioinformatics tools either require ChIP-seq datasets for both partner transcription factors, or omit composite elements with motifs overlapping. Here we present an universal Motifs Co-Occurrence Tool (MCOT) that retrieves maximum information about overrepresented composite elements from a single ChIP-seq dataset. This includes homo- and heterotypic composite elements of four mutual orientations of motifs, separated with a spacer or overlapping, even if recognition of motifs within composite element requires various stringencies. Analysis of 52 ChIP-seq datasets for 18 human transcription factors confirmed that for over 60% of analyzed datasets and transcription factors predicted co-occurrence of motifs implied experimentally proven protein-protein interaction of respecting transcription factors. Analysis of 164 ChIP-seq datasets for 57 mammalian transcription factors showed that abundance of predicted composite elements with an overlap of motifs compared to those with a spacer more than doubled; and they had 1.5-fold increase of asymmetrical pairs of motifs with one more conservative 'leading' motif and another one 'guided'.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkz800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868382PMC
December 2019

Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism.

Int J Mol Sci 2019 Sep 24;20(19). Epub 2019 Sep 24.

Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany.

The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of genes that are involved in metabolism under hypoxic conditions, but information regarding the transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1α was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly increased by (i) glutamine metabolism, which was associated with the release of ammonium, and it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1α only under normoxia. The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231 cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1 significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However, the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited the release of the amino acid alanine. This study comprehensively investigated, for the first time, how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently, the Warburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20194742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802203PMC
September 2019

Prediction of regulatory targets of alternative isoforms of the epidermal growth factor receptor in a glioblastoma cell line.

BMC Bioinformatics 2019 Aug 22;20(1):434. Epub 2019 Aug 22.

Institute of Computer Science, Martin Luther University Halle-Wittenberg, Halle, Germany.

Background: The epidermal growth factor receptor (EGFR) is a major regulator of proliferation in tumor cells. Elevated expression levels of EGFR are associated with prognosis and clinical outcomes of patients in a variety of tumor types. There are at least four splice variants of the mRNA encoding four protein isoforms of EGFR in humans, named I through IV. EGFR isoform I is the full-length protein, whereas isoforms II-IV are shorter protein isoforms. Nevertheless, all EGFR isoforms bind the epidermal growth factor (EGF). Although EGFR is an essential target of long-established and successful tumor therapeutics, the exact function and biomarker potential of alternative EGFR isoforms II-IV are unclear, motivating more in-depth analyses. Hence, we analyzed transcriptome data from glioblastoma cell line SF767 to predict target genes regulated by EGFR isoforms II-IV, but not by EGFR isoform I nor other receptors such as HER2, HER3, or HER4.

Results: We analyzed the differential expression of potential target genes in a glioblastoma cell line in two nested RNAi experimental conditions and one negative control, contrasting expression with EGF stimulation against expression without EGF stimulation. In one RNAi experiment, we selectively knocked down EGFR splice variant I, while in the other we knocked down all four EGFR splice variants, so the associated effects of EGFR II-IV knock-down can only be inferred indirectly. For this type of nested experimental design, we developed a two-step bioinformatics approach based on the Bayesian Information Criterion for predicting putative target genes of EGFR isoforms II-IV. Finally, we experimentally validated a set of six putative target genes, and we found that qPCR validations confirmed the predictions in all cases.

Conclusions: By performing RNAi experiments for three poorly investigated EGFR isoforms, we were able to successfully predict 1140 putative target genes specifically regulated by EGFR isoforms II-IV using the developed Bayesian Gene Selection Criterion (BGSC) approach. This approach is easily utilizable for the analysis of data of other nested experimental designs, and we provide an implementation in R that is easily adaptable to similar data or experimental designs together with all raw datasets used in this study in the BGSC repository, https://github.com/GrosseLab/BGSC .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12859-019-2944-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704634PMC
August 2019

Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro.

Nucleic Acids Res 2019 09;47(17):9343-9357

Institute of Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Halle/Saale D-06120, Germany.

In response to a viral infection, the plant's RNA silencing machinery processes viral RNAs into a huge number of small interfering RNAs (siRNAs). However, a very few of these siRNAs actually interfere with viral replication. A reliable approach to identify these immunologically effective siRNAs (esiRNAs) and to define the characteristics underlying their activity has not been available so far. Here, we develop a novel screening approach that enables a rapid functional identification of antiviral esiRNAs. Tests on the efficacy of such identified esiRNAs of a model virus achieved a virtual full protection of plants against a massive subsequent infection in transient applications. We find that the functionality of esiRNAs depends crucially on two properties: the binding affinity to Argonaute proteins and the ability to access the target RNA. The ability to rapidly identify functional esiRNAs could be of great benefit for all RNA silencing-based plant protection measures against viruses and other pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkz678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755098PMC
September 2019

RNA-Seq analysis of soft rush (Juncus effusus): transcriptome sequencing, de novo assembly, annotation, and polymorphism identification.

BMC Genomics 2019 Jun 13;20(1):489. Epub 2019 Jun 13.

Department of Community Ecology, Helmholtz Centre for Environmental Research - UFZ, Theodor-Lieser-Str. 4, 06120, Halle (Saale), Germany.

Background: Juncus effusus L. (family: Juncaceae; order: Poales) is a helophytic rush growing in temperate damp or wet terrestrial habitats and is of almost cosmopolitan distribution. The species has been studied intensively with respect to its interaction with co-occurring plants as well as microbes being involved in major biogeochemical cycles. J. effusus has biotechnological value as component of Constructed Wetlands where the plant has been employed in phytoremediation of contaminated water. Its genome has not been sequenced.

Results: In this study we carried out functional annotation and polymorphism analysis of de novo assembled RNA-Seq data from 18 genotypes using 249 million paired-end Illumina HiSeq reads and 2.8 million 454 Titanium reads. The assembly comprised 158,591 contigs with a mean contig length of 780 bp. The assembly was annotated using the dammit! annotation pipeline, which queries the databases OrthoDB, Pfam-A, Rfam, and runs BUSCO (Benchmarking Single-Copy Ortholog genes). In total, 111,567 contigs (70.3%) were annotated with functional descriptions, assigned gene ontology terms, and conserved protein domains, which resulted in 30,932 non-redundant gene sequences. Results of BUSCO and KEGG pathway analyses were similar for J. effusus as for the well-studied members of the Poales, Oryza sativa and Sorghum bicolor. A total of 566,433 polymorphisms were identified in transcribed regions with an average frequency of 1 polymorphism in every 171 bases.

Conclusions: The transcriptome assembly was of high quality and genome coverage was sufficient for global analyses. This annotated knowledge resource can be utilized for future gene expression analysis, genomic feature comparisons, genotyping, primer design, and functional genomics in J. effusus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-019-5886-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567414PMC
June 2019

Metabolic footprint and intestinal microbial changes in response to dietary proteins in a pig model.

J Nutr Biochem 2019 05 3;67:149-160. Epub 2019 Mar 3.

Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany. Electronic address:

Epidemiological studies revealed that dietary proteins can contribute to the modulation of the cardiovascular disease risk. Still, direct effects of dietary proteins on serum metabolites and other health-modulating factors have not been fully explored. Here, we compared the effects of dietary lupin protein with the effects of beef protein and casein on the serum metabolite profile, cardiovascular risk markers and the fecal microbiome. Pigs were fed diets containing 15% of the respective proteins for 4 weeks. A classification analysis of the serum metabolites revealed six biomarker sets of two metabolites each that discriminated between the intake of lupin protein, lean beef or casein. These biomarker sets included 1- and 3-methylhistidine, betaine, carnitine, homoarginine and methionine. The study revealed differences in the serum levels of the metabolites 1- and 3- methylhistidine, homoarginine, methionine and homocysteine, which are involved in the one-carbon cycle. However, these changes were not associated with differences in the methylation capacity or the histone methylation pattern. With the exception of serum homocysteine and homoarginine levels, other cardiovascular risk markers, such as the homeostatic model assessment index, trimethylamine-N-oxide and lipids, were not influenced by the dietary protein source. However, the composition of the fecal microorganisms was markedly changed by the dietary protein source. Lupin-protein-fed pigs exhibited more species from the phyla Bacteroidetes and Firmicutes than the other two groups. In conclusion, different dietary protein sources induce distinct serum metabolic fingerprints, have an impact on the cardiovascular risk and modulate the composition of the fecal microbiome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jnutbio.2019.02.004DOI Listing
May 2019

Allele specific chromatin signals, 3D interactions, and motif predictions for immune and B cell related diseases.

Sci Rep 2019 02 25;9(1):2695. Epub 2019 Feb 25.

Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

Several Genome Wide Association Studies (GWAS) have reported variants associated to immune diseases. However, the identified variants are rarely the drivers of the associations and the molecular mechanisms behind the genetic contributions remain poorly understood. ChIP-seq data for TFs and histone modifications provide snapshots of protein-DNA interactions allowing the identification of heterozygous SNPs showing significant allele specific signals (AS-SNPs). AS-SNPs can change a TF binding site resulting in altered gene regulation and are primary candidates to explain associations observed in GWAS and expression studies. We identified 17,293 unique AS-SNPs across 7 lymphoblastoid cell lines. In this set of cell lines we interrogated 85% of common genetic variants in the population for potential regulatory effect and we identified 237 AS-SNPs associated to immune GWAS traits and 714 to gene expression in B cells. To elucidate possible regulatory mechanisms we integrated long-range 3D interactions data to identify putative target genes and motif predictions to identify TFs whose binding may be affected by AS-SNPs yielding a collection of 173 AS-SNPs associated to gene expression and 60 to B cell related traits. We present a systems strategy to find functional gene regulatory variants, the TFs that bind differentially between alleles and novel strategies to detect the regulated genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-39633-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389883PMC
February 2019

Time resolved gene expression analysis during tamoxifen adaption of MCF-7 cells identifies long non-coding RNAs with prognostic impact.

RNA Biol 2019 05 5;16(5):661-674. Epub 2019 Mar 5.

d Institute of Pathology, Otto von Guericke University Magdeburg , Magdeburg , Germany.

Acquired tamoxifen resistance is a persistent problem for the treatment of estrogen receptor positive, premenopausal breast cancer patients and predictive biomarkers are still elusive. We here analyzed gene expression changes in a cellular model to identify early and late changes upon tamoxifen exposure and thereby novel prognostic biomarkers. Estrogen receptor positive MCF-7 cells were incubated with 4OH-tamoxifen (10 nM) and gene expression analyzed by array hybridization during 12 weeks. Array results were confirmed by nCounter- and qRT-PCR technique. Pathway enrichment analysis revealed that early responses concerned mainly amine synthesis and NRF2-related signaling and evolved into a stable gene expression pattern within 4 weeks characterized by changes in glucuronidation-, estrogen metabolism-, nuclear receptor- and interferon signaling pathways. As a large number of long non coding RNAs was subject to regulation, we investigated 5 of these (linc01213, linc00632 linc0992, LOC101929547 and XR_133213) in more detail. From these, only linc01213 was upregulated but all were less abundant in estrogen-receptor negative cell lines (MDA-MB 231, SKBR-3 and UACC3199). In a web-based survival analysis linc01213 and linc00632 turned out to have prognostic impact. Linc01213 was investigated further by plasmid-mediated over-expression as well as siRNA down-regulation in MCF-7 cells. Nevertheless, this had no effect on proliferation or expression of tamoxifen regulated genes, but migration was increased. In conclusion, the cellular model identified a set of lincRNAs with prognostic relevance for breast cancer. One of these, linc01213 although regulated by 4OH-tamoxifen, is not a central regulator of tamoxifen adaption, but interferes with the regulation of migration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15476286.2019.1581597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546408PMC
May 2019

Comparison of the oral microbiome of patients with generalized aggressive periodontitis and periodontitis-free subjects.

Arch Oral Biol 2019 Mar 28;99:169-176. Epub 2019 Jan 28.

Department of Operative Dentistry and Periodontology, Martin Luther University Halle-Wittenberg, Germany.

Objective: The primary objectives of the study were to assess differences in complex subgingival bacterial composition between periodontitis-free persons and patients with generalized aggressive periodontitis (gAgP).

Background: The composition of the oral microbiota plays an important role for both oral and systemic diseases. However, the complex nature of the oral microbiome and its homeostasis is still poorly understood.

Material And Methods: We compared the microbiome of 13 periodontitis-free persons to 13 patients with gAgP. The 16S rRNA genes were amplified, targeting the V3/V4 region using the MiSeq platform.

Results: In total, 1713 different bacterial species were mapped according to the Greengenes database. Using the Shannon index, no significant differences in alpha diversity were found between the two study groups. In principal component and linear discriminant analyses, disease-specific differences in beta diversity of the microbiome composition were evaluated. Bacteroidetes, Spirochaetes, and Synergistetes were more abundant in gAgP whereas Proteobacteria, Firmicutes, and Actinobacteria were associated with a healthy periodontium. At the bacterial species level, we showed that Porphyromonas gingivalis is the strongest indicator of gAgP. Treponema denticola and Tanerella forsythia of the "red complex" as well as Filifactor alocis were among the ten best biomarkers for gAgP.

Conclusions: These results broaden our knowledge of disease-specific differences in the microbial community associated with generalized AgP. A more complex view of the composition of the oral microbiome describes the etiology of generalized AgP in more detail. These results could help to individually adapt periodontal therapy in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2019.01.015DOI Listing
March 2019

WebHERV: A Web Server for the Computational Investigation of Gene Expression Associated With Endogenous Retrovirus-Like Sequences.

Front Microbiol 2018 5;9:2384. Epub 2018 Nov 5.

Institute of Computer Science, Martin Luther University Halle-Wittenberg, Halle, Germany.

More than eight percent of the human genome consists of human endogenous retroviruses (HERVs). Typically, the expression of HERVs is repressed, but varying activities of HERVs have been observed in diseases ranging from cancer to neuro-degeneration. Such activities can include the transcription of HERV-derived open reading frames, which can be translated into proteins. However, as a consequence of mutations that disrupt open reading frames, most HERV-like sequences have lost their protein-coding capacity. Nevertheless, these loci can still influence the expression of adjacent genes and, hence, mediate biological effects. Here, we present WebHERV (http://calypso.informatik.uni-halle.de/WebHERV/), a web server that enables the computational prediction of active HERV-like sequences in the human genome based on a comparison of genome coordinates of expressed sequences uploaded by the user and genome coordinates of HERV-like sequences stored in the specialized key-value store DRUMS. Using WebHERV, we predicted putative candidates of active HERV-like sequences in Hodgkin lymphoma (HL) cell lines, validated one of them by a modified SMART (switching mechanism at 5' end of RNA template) technique, and identified a new alternative transcription start site for cytochrome P450, family 4, subfamily Z, polypeptide 1 (CYP4Z1).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2018.02384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231192PMC
November 2018

EFFECTOR OF TRANSCRIPTION factors are novel plant-specific regulators associated with genomic DNA methylation in Arabidopsis.

New Phytol 2019 01 25;221(1):261-278. Epub 2018 Sep 25.

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), 06466, Seeland OT Gatersleben, Germany.

Plant-specific EFFECTORS OF TRANSCRIPTION (ET) are characterised by a variable number of highly conserved ET repeats, which are involved in zinc and DNA binding. In addition, ETs share a GIY-YIG domain, involved in DNA nicking activity. It was hypothesised that ETs might act as epigenetic regulators. Here, methylome, transcriptome and phenotypic analyses were performed to investigate the role of ET factors and their involvement in DNA methylation in Arabidopsis thaliana. Comparative DNA methylation and transcriptome analyses in flowers and seedlings of et mutants revealed ET-specific differentially expressed genes and mostly independently characteristic, ET-specific differentially methylated regions. Loss of ET function results in pleiotropic developmental defects. The accumulation of cyclobutane pyrimidine dimers after ultraviolet stress in et mutants suggests an ET function in DNA repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nph.15439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585611PMC
January 2019

Age- and Diabetes-Related Changes in the Free Fatty Acid Composition of the Human Stratum Corneum.

Skin Pharmacol Physiol 2018 21;31(6):283-291. Epub 2018 Aug 21.

Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Of particular importance for Stratum corneum (SC) lipids are the free fatty acids (FFAs). Age-related changes of the SC structure lead to diminished capacity for barrier compensation. The aims of this cross-sectional study were to identify even-numbered especially odd-numbered FFAs within the intercorneocytic lamellar lipid structures of the SC and to explore age- and diabetes-related changes in FFAs. Gas chromatography - flame ionisation detection was used to qualitatively and quantitatively assess FFAs extracted from the SC. 110 subjects aged over 60 years (elderly/healthy), 110 subjects aged 18-40 (young/healthy) and 38 subjects with diabetes mellitus aged 18-40 (young/diabetic) were investigated. Overall, odd-numbered FFAs comprised about 21, 23 and 24% of total FFAs in subgroups elderly/healthy, young/healthy and young/diabetic. The most abundant short-chain FFAs were C16: 0 and C18: 0 and long-chain FFAs were C24: 0 and C26: 0. Only levels of C15: 0 and C17: 0 decreased with age. In contrast, levels of C18: 2 and C19 were significantly decreased and levels of C15, C17, C18: 1 and C23 were significantly increased in young diabetic subjects. In general, compared with younger healthy subjects, FFA composition was only partly significantly altered in older healthy subjects but was significantly altered in younger diabetic subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000490800DOI Listing
November 2018

Whole-transcriptome analysis reveals genetic factors underlying flowering time regulation in rapeseed (Brassica napus L.).

Plant Cell Environ 2018 08 19;41(8):1935-1947. Epub 2018 Jun 19.

Plant Breeding Institute, Christian-Albrechts-University of Kiel, Kiel, Germany.

Rapeseed (Brassica napus L.), one of the most important sources of vegetable oil and protein-rich meals worldwide, is adapted to different geographical regions by modification of flowering time. Rapeseed cultivars have different day length and vernalization requirements, which categorize them into winter, spring, and semiwinter ecotypes. To gain a deeper insight into genetic factors controlling floral transition in B. napus, we performed RNA sequencing (RNA-seq) in the semiwinter doubled haploid line, Ningyou7, at different developmental stages and temperature regimes. The expression profiles of more than 54,000 gene models were compared between different treatments and developmental stages, and the differentially expressed genes were considered as targets for association analysis and genetic mapping to confirm their role in floral transition. Consequently, 36 genes with association to flowering time, seed yield, or both were identified. We found novel indications for neofunctionalization in homologs of known flowering time regulators like VIN3 and FUL. Our study proved the potential of RNA-seq along with association analysis and genetic mapping to identify candidate genes for floral transition in rapeseed. The candidate genes identified in this study could be subjected to genetic modification or targeted mutagenesis and genotype building to breed rapeseed adapted to certain environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pce.13353DOI Listing
August 2018

A Viral Suppressor Modulates the Plant Immune Response Early in Infection by Regulating MicroRNA Activity.

mBio 2018 04 24;9(2). Epub 2018 Apr 24.

Institute of Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany

Many viral suppressors (VSRs) counteract antiviral RNA silencing, a central component of the plant's immune response by sequestration of virus-derived antiviral small interfering RNAs (siRNAs). Here, we addressed how VSRs affect the activities of cellular microRNAs (miRNAs) during a viral infection by characterizing the interactions of two unrelated VSRs, the p19 and the 2b, with miRNA 162 (miR162), miR168, and miR403. These miRNAs regulate the expression of the important silencing factors Dicer-like protein 1 (DCL1) and Argonaute proteins 1 and 2 (AGO1 and AGO2), respectively. Interestingly, while the two VSRs showed similar binding profiles, the miRNAs were bound with significantly different affinities, for example, with the affinity of miR162 greatly exceeding that of miR168. silencing experiments revealed that p19 and 2b affect miRNA-mediated silencing of the , , and mRNAs in strict accordance with the VSR's miRNA-binding profiles. In -infected plants, the miRNA-binding behavior of p19 closely corresponded to that Most importantly, in contrast to controls with a Δp19 virus, infections with wild-type (wt) virus led to changes of the levels of the miRNA-targeted mRNAs, and these changes correlated with the miRNA-binding preferences of p19. This was observed exclusively in the early stage of infection when viral genomes are proposed to be susceptible to silencing and viral siRNA (vsiRNA) concentrations are low. Accordingly, our study suggests that differential binding of miRNAs by VSRs is a widespread viral mechanism to coordinately modulate cellular gene expression and the antiviral immune response during infection initiation. Plant viruses manipulate their hosts in various ways. Viral suppressor proteins (VSRs) interfere with the plant's immune response by sequestering small, antivirally acting vsiRNAs, which are processed from viral RNAs during the plant's RNA-silencing response. Here, we examined the effects of VSRs on cellular microRNAs (miRNAs), which show a high degree of similarity with vsiRNAs. Binding experiments with two unrelated VSRs and three important regulatory miRNAs revealed that the proteins exhibit similar miRNA-binding profiles but bind different miRNAs at considerably different affinities. Most interestingly, experiments in plants showed that in the early infection phase, the VSR p19 modulates the activity of these miRNAs on their target mRNAs very differently and that this differential regulation strictly correlates with the binding affinities of p19 for the respective miRNAs. Our data suggest that VSRs may specifically control plant gene expression and the early immune response by differential sequestration of miRNAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.00419-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915741PMC
April 2018

Genome-wide single nucleotide polymorphism scan suggests adaptation to urbanization in an important pollinator, the red-tailed bumblebee ( L.).

Proc Biol Sci 2018 04;285(1877)

General Zoology, Institute of Biology, Martin Luther University Halle-Wittenberg, Hoher Weg 8, 06120 Halle (Saale), Germany.

Urbanization is considered a global threat to biodiversity; the growth of cities results in an increase in impervious surfaces, soil and air pollution, fragmentation of natural vegetation and invasion of non-native species, along with numerous environmental changes, including the heat island phenomenon. The combination of these effects constitutes a challenge for both the survival and persistence of many native species, while also imposing altered selective regimes. Here, using 110 314 single nucleotide polymorphisms generated by restriction-site-associated DNA sequencing, we investigated the genome-wide effects of urbanization on putative neutral and adaptive genomic diversity in a major insect pollinator, , collected from nine German cities and nine paired rural sites. Overall, genetic differentiation among sites was low and there was no obvious genome-wide genetic structuring, suggesting the absence of strong effects of urbanization on gene flow. We nevertheless identified several loci under directional selection, a subset of which was associated with urban land use, including the percentage of impervious surface surrounding each sampling site. Overall, our results provide evidence of local adaptation to urbanization in the face of gene flow in a highly mobile insect pollinator.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rspb.2017.2806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936727PMC
April 2018

Transcriptome dynamics at graft junctions reveal an intertissue recognition mechanism that activates vascular regeneration.

Proc Natl Acad Sci U S A 2018 03 13;115(10):E2447-E2456. Epub 2018 Feb 13.

Sainsbury Laboratory, University of Cambridge, Cambridge CB2 1LR, United Kingdom.

The ability for cut tissues to join and form a chimeric organism is a remarkable property of many plants; however, grafting is poorly characterized at the molecular level. To better understand this process, we monitored genome-wide gene expression changes in grafted hypocotyls. We observed a sequential activation of genes associated with cambium, phloem, and xylem formation. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than on the other. This asymmetry correlated with sugar-responsive genes, and we observed an accumulation of starch above the graft junction. This accumulation decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues, indicating that a recognition mechanism was activated independently of functional vascular connections. Auxin, which is transported cell to cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes was expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, intertissue communication, and tissue fusion events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1718263115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878008PMC
March 2018

myTAI: evolutionary transcriptomics with R.

Bioinformatics 2018 05;34(9):1589-1590

Institute of Computer Science, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany.

Motivation: Next Generation Sequencing (NGS) technologies generate a large amount of high quality transcriptome datasets enabling the investigation of molecular processes on a genomic and metagenomic scale. These transcriptomics studies aim to quantify and compare the molecular phenotypes of the biological processes at hand. Despite the vast increase of available transcriptome datasets, little is known about the evolutionary conservation of those characterized transcriptomes.

Results: The myTAI package implements exploratory analysis functions to infer transcriptome conservation patterns in any transcriptome dataset. Comprehensive documentation of myTAI functions and tutorial vignettes provide step-by-step instructions on how to use the package in an exploratory and computationally reproducible manner.

Availability And Implementation: The open source myTAI package is available at https://github.com/HajkD/myTAI and https://cran.r-project.org/web/packages/myTAI/index.html.

Contact: hgd23@cam.ac.uk.

Supplementary Information: Supplementary data are available at Bioinformatics online.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/bioinformatics/btx835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5925770PMC
May 2018

Adaptation of iCLIP to plants determines the binding landscape of the clock-regulated RNA-binding protein AtGRP7.

Genome Biol 2017 10 31;18(1):204. Epub 2017 Oct 31.

RNA Biology and Molecular Physiology, Faculty of Biology, Bielefeld University, Bielefeld, Germany.

Background: Functions for RNA-binding proteins in orchestrating plant development and environmental responses are well established. However, the lack of a genome-wide view of their in vivo binding targets and binding landscapes represents a gap in understanding the mode of action of plant RNA-binding proteins. Here, we adapt individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP) genome-wide to determine the binding repertoire of the circadian clock-regulated Arabidopsis thaliana glycine-rich RNA-binding protein AtGRP7.

Results: iCLIP identifies 858 transcripts with significantly enriched crosslink sites in plants expressing AtGRP7-GFP that are absent in plants expressing an RNA-binding-dead AtGRP7 variant or GFP alone. To independently validate the targets, we performed RNA immunoprecipitation (RIP)-sequencing of AtGRP7-GFP plants subjected to formaldehyde fixation. Of the iCLIP targets, 452 were also identified by RIP-seq and represent a set of high-confidence binders. AtGRP7 can bind to all transcript regions, with a preference for 3' untranslated regions. In the vicinity of crosslink sites, U/C-rich motifs are overrepresented. Cross-referencing the targets against transcriptome changes in AtGRP7 loss-of-function mutants or AtGRP7-overexpressing plants reveals a predominantly negative effect of AtGRP7 on its targets. In particular, elevated AtGRP7 levels lead to damping of circadian oscillations of transcripts, including DORMANCY/AUXIN ASSOCIATED FAMILY PROTEIN2 and CCR-LIKE. Furthermore, several targets show changes in alternative splicing or polyadenylation in response to altered AtGRP7 levels.

Conclusions: We have established iCLIP for plants to identify target transcripts of the RNA-binding protein AtGRP7. This paves the way to investigate the dynamics of posttranscriptional networks in response to exogenous and endogenous cues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-017-1332-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663106PMC
October 2017

Ecological plant epigenetics: Evidence from model and non-model species, and the way forward.

Ecol Lett 2017 Dec 12;20(12):1576-1590. Epub 2017 Oct 12.

Netherlands Institute of Ecology (NIOO-KNAW), Wageningen, The Netherlands.

Growing evidence shows that epigenetic mechanisms contribute to complex traits, with implications across many fields of biology. In plant ecology, recent studies have attempted to merge ecological experiments with epigenetic analyses to elucidate the contribution of epigenetics to plant phenotypes, stress responses, adaptation to habitat, and range distributions. While there has been some progress in revealing the role of epigenetics in ecological processes, studies with non-model species have so far been limited to describing broad patterns based on anonymous markers of DNA methylation. In contrast, studies with model species have benefited from powerful genomic resources, which contribute to a more mechanistic understanding but have limited ecological realism. Understanding the significance of epigenetics for plant ecology requires increased transfer of knowledge and methods from model species research to genomes of evolutionarily divergent species, and examination of responses to complex natural environments at a more mechanistic level. This requires transforming genomics tools specifically for studying non-model species, which is challenging given the large and often polyploid genomes of plants. Collaboration among molecular geneticists, ecologists and bioinformaticians promises to enhance our understanding of the mutual links between genome function and ecological processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ele.12858DOI Listing
December 2017

Diversity of cis-regulatory elements associated with auxin response in Arabidopsis thaliana.

J Exp Bot 2018 01;69(2):329-339

Novosibirsk State University, Russian Federation.

The phytohormone auxin regulates virtually every developmental process in land plants. This regulation is mediated via de-repression of DNA-binding auxin response factors (ARFs). ARFs bind TGTC-containing auxin response cis-elements (AuxREs), but there is growing evidence that additional cis-elements occur in auxin-responsive regulatory regions. The repertoire of auxin-related cis-elements and their involvement in different modes of auxin response are not yet known. Here we analyze the enrichment of nucleotide hexamers in upstream regions of auxin-responsive genes associated with auxin up- or down-regulation, with early or late response, ARF-binding domains, and with different chromatin states. Intriguingly, hexamers potentially bound by basic helix-loop-helix (bHLH) and basic leucine zipper (bZIP) factors as well as a family of A/T-rich hexamers are more highly enriched in auxin-responsive regions than canonical TGTC-containing AuxREs. We classify and annotate the whole spectrum of enriched hexamers and discuss their patterns of enrichment related to different modes of auxin response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jxb/erx254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853796PMC
January 2018

Optimal Block-Based Trimming for Next Generation Sequencing.

IEEE/ACM Trans Comput Biol Bioinform 2018 Mar-Apr;15(2):364-376. Epub 2017 Apr 24.

Read trimming is a fundamental first step of the analysis of next generation sequencing (NGS) data. Traditionally, it is performed heuristically, and algorithmic work in this area has been neglected. Here, we address this topic and formulate three optimization problems for block-based trimming (truncating the same low-quality positions at both ends for all reads and removing low-quality truncated reads). We find that all problems are NP-hard. Hence, we investigate the approximability of the problems. Two of them are NP-hard to approximate. However, the non-random distribution of quality scores in NGS data sets makes it tempting to speculate that quality constraints for read positions are typically satisfied by fulfilling quality constraints for reads. Thus, we propose three relaxed problems and develop efficient polynomial-time algorithms for them including heuristic speed-up techniques and parallelizations. We apply these optimized block trimming algorithms to 12 data sets from three species, four sequencers, and read lengths ranging from 36 to 101 bp and find that (i) the omitted constraints are indeed almost always satisfied, (ii) the optimized read trimming algorithms typically yield a higher number of untrimmed bases than traditional heuristics, and (iii) these results can be generalized to alternative objective functions beyond counting the number of untrimmed bases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCBB.2017.2696525DOI Listing
February 2019

Cross-kingdom comparison of the developmental hourglass.

Curr Opin Genet Dev 2017 Aug 24;45:69-75. Epub 2017 Mar 24.

Martin Luther University Halle-Wittenberg, Institute of Agricultural and Nutritional Sciences, Betty-Heimann-Str. 5, 06120 Halle (Saale), Germany. Electronic address:

The developmental hourglass model has its foundations in classic anatomical studies by von Baer and Haeckel. In this context, even the conservation of animal body plans has been explained by evolutionary constraints acting on mid-embryogenic development. Recent studies have shown that developmental hourglass patterns also exist on the transcriptomic level, mirroring the corresponding morphological patterns. The identification of similar patterns in embryonic, post-embryonic, and life cycle spanning transcriptomes in plant and fungus development, however, contradict the notion of a direct coupling between morphological and molecular patterns. To explain the existence of hourglass patterns across kingdoms and developmental processes, we propose the organizational checkpoint model that integrates the developmental hourglass model into a framework of transcriptome switches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gde.2017.03.003DOI Listing
August 2017