Publications by authors named "David P Kreil"

Next-generation sequencing (NGS) has revolutionized genomic research by enabling high-throughput, cost-effective genome and transcriptome sequencing accelerating personalized medicine for complex diseases, including cancer. Whole genome/transcriptome sequencing (WGS/WTS) provides comprehensive insights, while targeted sequencing is more cost-effective and sensitive. In comparison to short-read sequencing, which still dominates the field due to high speed and cost-effectiveness, long-read sequencing can overcome alignment limitations and better discriminate similar sequences from alternative transcripts or repetitive regions.

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Mycoparasitism is a key feature of Trichoderma (Hypocreales, Ascomycota) biocontrol agents. Recent studies of intracellular signal transduction pathways of the potent mycoparasite Trichoderma atroviride revealed the involvement of Tmk1, a mitogen-activated protein kinase (MAPK), in triggering the mycoparasitic response. We previously showed that mutants missing Tmk1 exhibit reduced mycoparasitic activity against several plant pathogenic fungi.

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With more and more data being collected, modern network representations exploit the complementary nature of different data sources as well as similarities across patients. We here introduce the Variation of information fused Layers of Networks algorithm (ViLoN), a novel network-based approach for the integration of multiple molecular profiles. As a key innovation, it directly incorporates prior functional knowledge (KEGG, GO).

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Background: Silicone breast implants with smooth outer shells are associated with higher rates of capsular contracture, whereas textured implants have been linked to the development of breast implant-associated anaplastic large cell lymphoma. By assessing the gene expression profile of fibrous capsules formed in response to smooth and textured implants, insight into the development of breast implant-associated abnormalities can be gained.

Methods: Miniature smooth or textured silicone implants were surgically inserted into female rats ( n = 10) and harvested for the surrounding capsules at postoperative week 6.

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Berry shrivel (BS) is one of the prominent and still unresolved ripening physiological disorders in grapevine. The causes of BS are unclear, and previous studies focused on the berry metabolism or histological studies, including cell viability staining in the rachis and berries of BS clusters. Herein, we studied the transcriptional modulation induced by BS in the rachis of pre-symptomatic and symptomatic clusters with a custom-made microarray qPCR in relation to a previous RNASeq study of BS berries.

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Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury.

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Background: Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance.

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Background: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S.

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The rat is an important model organism in biomedical research for studying human disease mechanisms and treatments, but its annotated transcriptome is far from complete. We constructed a Rat Transcriptome Re-annotation named RTR using RNA-seq data from 320 samples in 11 different organs generated by the SEQC consortium. Totally, there are 52 807 genes and 114 152 transcripts in RTR.

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Objective: To assess gene expression in cardiomyocytes isolated from patients with aortic stenosis, hypothesizing that maladaptive remodeling and inflammation-related genes are higher in male vs female patients.

Patients And Methods: In this study, 34 patients with aortic stenosis undergoing aortic valve replacement from March 20, 2016, through May 24, 2017, at the German Heart Centre in Berlin, Germany, were included. Isolated cardiomyocytes from interventricular septum samples were used for gene expression analysis.

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Modifications of ribosomal RNA expand the nucleotide repertoire and thereby contribute to ribosome heterogeneity and translational regulation of gene expression. One particular m5C modification of 25S ribosomal RNA, which is introduced by Rcm1p, was previously shown to modulate stress responses and lifespan in yeast and other small organisms. Here, we report that NSUN5 is the functional orthologue of Rcm1p, introducing m5C3782 into human and m5C3438 into mouse 28S ribosomal RNA.

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RNA sequencing (RNA-seq) has greatly facilitated the exploring of transcriptome landscape for diverse organisms. However, transcriptome reconstruction is still challenging due to various limitations of current tools and sequencing technologies. Here, we introduce an efficient tool, QuaPra (Quadratic Programming combined with Apriori), for accurate transcriptome assembly and quantification.

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Mycoparasites, e.g. fungi feeding on other fungi, are prominent within the genus Trichoderma and represent a promising alternative to chemical fungicides for plant disease control.

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Article Synopsis
  • * Fetal mammals can heal their cartilage better than adults can, especially during early development stages.
  • * The study compared how fetal and adult sheep respond to cartilage injury and found some important proteins that could help us figure out new treatments for adults with OA.
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Chinese Hamster Ovary (CHO) cells are the preferred cell line for production of biopharmaceuticals. These cells are capable to grow without serum supplementation, but drastic changes in their phenotype occur during adaptation to protein-free growth, which typically include the change to a suspension phenotype with reduced growth rate. A possible approach to understand this transformation, with the intention to counteract the reduction in growth by targeted supplementation of protein-free media, is gene expression profiling.

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Background: The MAQC/SEQC consortium has recently compiled a key benchmark that can serve for testing the latest developments in analysis tools for microarray and RNA-seq expression profiling. Such objective benchmarks are required for basic and applied research, and can be critical for clinical and regulatory outcomes. Going beyond the first comparisons presented in the original SEQC study, we here present extended benchmarks including effect strengths typical of common experiments.

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Several biologically active peptides contain a d- amino acid in a well-defined position, which is position 2 in all peptide epimers isolated to date from vertebrates and also some from invertebrates. The detection of such D- residues by standard analytical techniques is challenging. In tandem mass spectrometric (MS) analysis, although fragment masses are the same for all stereoisomers, peak intensities are known to depend on chirality.

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Over the last three decades, product yields from CHO cells have increased dramatically, yet specific productivity (qP) remains a limiting factor. In a previous study, using repeated cell-sorting, we have established different host cell subclones that show superior transient qP over their respective parental cell lines (CHO-K1, CHO-S). The transcriptome of the resulting six cell lines in different biological states (untransfected, mock transfected, plasmid transfected) was first explored by hierarchical clustering and indicated that gene activity associated with increased qP did not stem from a certain cellular state but seemed to be inherent for a high qP host line.

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Article Synopsis
  • - High-throughput technologies like next-generation sequencing have increased the data intensity in molecular biology, necessitating bioinformaticians to leverage high-performance computing for managing and analyzing large datasets.
  • - Workflow systems could simplify the creation of bioinformatics pipelines, automating tasks and enhancing reproducibility, but their complexity often leads to many pipelines being developed without them.
  • - The EU COST action SeqAhead hackathons revealed that different organizations tackling similar bioinformatics challenges often use varied and incompatible approaches, prompting the need for recommendations to create more efficient and user-friendly workflow systems.
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Purpose: To compare current imaging methods with respect to their ability to detect the condition of the fovea in patients with geographic atrophy (GA).

Methods: The retinas of 176 eyes with GA were imaged using two spectral-domain optical coherence tomography (SD-OCT) systems, Cirrus HD-OCT and Spectralis HRA+OCT, and fundus autofluorescence (FAF) and infrared imaging (IR) was used in the scanning laser ophthalmoscope (SLO) mode. Polarization-sensitive OCT (PS-OCT), which selectively visualizes the RPE in addition to SD-OCT features, was used to image 95 eyes.

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There is a critical need for standard approaches to assess, report and compare the technical performance of genome-scale differential gene expression experiments. Here we assess technical performance with a proposed standard 'dashboard' of metrics derived from analysis of external spike-in RNA control ratio mixtures. These control ratio mixtures with defined abundance ratios enable assessment of diagnostic performance of differentially expressed transcript lists, limit of detection of ratio (LODR) estimates and expression ratio variability and measurement bias.

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Article Synopsis
  • The study compares RNA-sequencing (RNA-seq) and microarrays for analyzing gene expression in liver samples from rats exposed to various chemicals.
  • Results show a strong correlation between the two methods, particularly in identifying differentially expressed genes (DEGs), but RNA-seq was more accurate overall, especially for low-abundance transcripts.
  • The findings highlight that factors like treatment effect size, transcript abundance, and biological complexity influence the effectiveness of transcriptomic research in clinical and regulatory contexts.
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