Ulf Schmitz

Verified

Ulf verified their affiliation via an institutional email.

Learn more

Verified

Ulf verified their affiliation via an institutional email.

Learn more

• Doctor of Engineering
• Professor (Associate) at James Cook University

Purpose of Review Long-read sequencing (LRS) has revolutionized pathogen surveillance by enabling real-time, high-fidelity genomic analysis critical for outbreak response. This review synthesizes recent breakthroughs in LRS, evaluating its impact on genomic epidemiology, metagenomics, and public health decision-making while addressing limitations a...

Extensive research into gene fusions in cancer and other diseases has led to the discovery of novel biomarkers and therapeutic targets. Concurrently, various bioinformatics tools have been developed for fusion detection in RNA sequencing data, which, in the age of increasing affordability of sequencing, have delivered a large-scale identification o...

Background The targeted application of cutting-edge high-throughput molecular data technologies provides an enormous opportunity to address key health, economic and environmental issues in the tropics within the One Health framework. The Earth’s tropical regions are projected to contain > 50% of the world’s population by 2050 coupled with 80% of it...

Alternative splicing (AS) is a crucial mechanism for regulating gene expression and isoform diversity in eukaryotes. However, the analysis and visualization of AS events from RNA sequencing data remains challenging. Most tools require a certain level of computer literacy and the available means of visualizing AS events, such as coverage and sashimi...

Cancer is a heterogeneous disease with a strong genetic component making it suitable for precision medicine approaches aimed at identifying the underlying molecular drivers within a tumour. Large scale population-level cancer sequencing consortia have identified many actionable mutations common across both cancer types and sub-types, resulting in a...

Long-read DNA sequencing technologies have been rapidly evolving in recent years, and their ability to assess large and complex regions of the genome makes them ideal for clinical applications in molecular diagnosis and therapy selection, thereby providing a valuable tool for precision medicine. In the third-generation sequencing duopoly, Oxford Na...

Purpose To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects. Patients and methods In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other s...

The microsatellite stable/epithelial-mesenchymal transition (MSS/EMT) subtype of gastric cancer represents a highly aggressive class of tumors associated with low rates of survival and considerably high probabilities of recurrence. In the era of precision medicine, the accurate and prompt diagnosis of tumors of this subtype is of vital importance....

Single-cell sequencing technologies have revolutionised the life sciences and biomedical research. Single-cell sequencing provides high-resolution data on cell heterogeneity, allowing high-fidelity cell type identification, and lineage tracking. Computational algorithms and mathematical models have been developed to make sense of the data, compensa...

Background After many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR, and such patterns have been pursued as both biomarkers and the...

Extensive investigation of gene fusions in cancer has led to the discovery of novel biomarkers and therapeutic targets. To date, most studies have neglected chromosomal rearrangement-independent fusion transcripts and complex fusion structures such as double or triple-hop fusions, and fusion-circRNAs. In this review, we untangle fusion-related term...

This book provides an update on the latest development in the field of microRNAs in cancer research with an emphasis on translational research. Since the early 2000s, microRNAs have been recognized as important and ubiquitous regulators of gene expression. Soon it became evident that their deregulation can cause human diseases including cancer. Thi...

Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including several cancers. Despite consistent reports demonstrating that intrinsic sequence features can help introns evade splicing, conflicting findings about cell type- or condition-specific IR regulati...

Despite an abundance of publicly available RNA sequencing datasets, a lack of integrated user-friendly tools hinder exploration of alternative splicing. SpliceWiz is an innovative, ultra-fast graphical R application that accurately quantifies splicing events using isoform-specific alignments. It is designed to accommodate hundreds of samples typica...

Recent landmark discoveries have underpinned the physiological importance of intron retention (IR) across multiple domains of life and revealed an unexpected breath of functions in a large variety of biological processes. Despite significant progress in the field, some challenges remain. Once solved, opportunities will arise for discovering more fu...

After many years of neglect in the field of alternative splicing, the importance of intron retention (IR) in cancer has come into focus following landmark discoveries of aberrant IR patterns in cancer. Many solid and liquid tumours are associated with drastic increases in IR and such patterns have been pursued as both biomarkers and therapeutic tar...

CCCTC-binding factor (CTCF) plays fundamental roles in transcriptional regulation and chromatin architecture maintenance. CTCF is also a tumour suppressor frequently mutated in cancer, however, the structural and functional impact of mutations have not been examined. We performed molecular and structural characterisation of five cancer-specific CTC...

S ummary In pancreatic cancer, emerging evidence suggests that PPAR-δ overexpression is associated with tumor progression and metastasis, but a mechanistic link is still missing. Here we now show that PPAR-δ acts as the integrating upstream regulator for the metabolic rewiring, which is preceding the subsequent initiation of an invasive/metastatic...

Chimeric RNAs are often associated with chromosomal rearrangements in cancer. In addition, they are also widely detected in normal tissues, contributing to transcriptomic complexity. Despite their prevalence, little is known about the characteristics and functions of chimeric RNAs. Here, we examine the genetic structure and biological roles of CLEC...

It is becoming evident that holistic perspectives toward cancer are crucial in deciphering the overwhelming complexity of tumors. Single-layer analysis of genome-wide data has greatly contributed to our understanding of cellular systems and their perturbations. However, fundamental gaps in our knowledge persist and hamper the design of effective in...

Three decades of research have established the CCCTC-binding factor (CTCF) as a ubiquitously expressed chromatin organizing factor and master regulator of gene expression. A new role for CTCF as a regulator of alternative splicing (AS) has now emerged. CTCF has been directly and indirectly linked to the modulation of AS at the individual transcript...

Background The phenomenon of widespread and dynamic intron retention (IR) programs in cells of vertebrate species has recently gained increasing attention. It has been shown that IR is involved in a multitude of cell-physiological processes, while aberrant IR profiles have been associated with numerous human diseases including several cancers. Gap...

CCCTC-binding factor (CTCF) plays fundamental roles in transcriptional regulation and chromatin architecture maintenance. CTCF is also a tumour suppressor frequently mutated in cancer, however the structural and functional impact of mutations have not been examined. We performed molecular and structural characterisation of 5 CTCF missense zinc fing...

Background Human cancers commonly contain mutations in transcription factors that lead to aberrant DNA binding or altered effector function at target sites. One such factor significantly mutated in cancer is the evolutionarily-conserved CCCTC-binding factor (CTCF), which has fundamental roles in maintaining chromatin architecture and transcriptiona...

Vast transcriptomics and epigenomics changes are characteristic of human cancers, including leukaemia. At remission, we assume that these changes normalise so that omics-profiles resemble those of healthy individuals. However, an in-depth transcriptomic and epigenomic analysis of cancer remission has not been undertaken. A striking exemplar of targ...

Intron retention (IR) in cancer was for a long time overlooked by the scientific community, as it was previously considered to be an artefact of a dysfunctional spliceosome. Technological advancements made in the last decade offer unique opportunities to explore the role of IR as a widespread phenomenon that contributes to the transcriptional diver...

Programmed cell death-ligand 1 (PD-L1) has recently been shown to play a role in the regulation of epithelial-to-mesenchymal transition (EMT); however, the relationship between PD-L1 expression, EMT and the inflammatory tumour microenvironment has yet to be investigated in thyroid cancer. To address this issue, we examined the expression of CD8, PD...

CTCF is a master regulator of gene transcription and chromatin organisation with occupancy at thousands of DNA target sites genome-wide. While CTCF is essential for cell survival, CTCF haploinsufficiency is associated with tumour development and hypermethylation. Increasing evidence demonstrates CTCF as a key player in several mechanisms regulating...

Background Vast transcriptomics and epigenomics changes are characteristic of human cancers including leukemia. At remission, we assume that these changes normalise so that omics-profiles resemble those of healthy individuals. However, an in-depth transcriptomic and epigenomic analysis of cancer remission has not been undertaken. A striking exempla...

Background: Survival from melanoma is strongly related to patient sex, with females having a survival rate almost twice that of males. Many explanations have been proposed but have not withstood critical scrutiny. Prior analysis of different cancers with a sex bias has identified six X-linked genes that escape X chromosome inactivation in females...

Background: Programmed cell death-ligand 1 (PD-L1) has recently been shown to play a role in the regulation of epithelial-to-mesenchymal transition (EMT) in some cancers. However, the relationship between PD-L1 expression, EMT and the inflammatory tumour microenvironment has yet to be investigated in thyroid cancer. Methods: To address this issue,...

Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using Illumina mRNA sequencing, Nanopore direct cDNA sequencing and proteomics analysis, we identify IR events that affect the expression of key genes/pr...

Alternative splicing is a ubiquitous process that increases transcriptomic and proteomic complexity across the animal kingdom. Intron retention (IR) is a particular form of alternative splicing that is different from the other forms as it only increases transcriptomic complexity but rarely directly affects the proteome. IR has long been neglected a...

CTCF is a master regulator of gene transcription and chromatin organization with occupancy at thousands of DNA target sites. CTCF is essential for embryonic development and somatic cell viability and has been characterized as a haploinsufficient tumor suppressor. Increasing evidence demonstrates CTCF as a key player in several alternative splicing...

Intron retention (IR) is a form of alternative splicing that has long been neglected in mammalian systems although it has been studied for decades in non-mammalian species such as plants, fungi, insects and viruses. It was generally assumed that mis-splicing, leading to the retention of introns, would have no physiological consequence other than re...

Colorectal cancer (CRC) results from a transformation of colonic epithelial cells into adenocarcinoma cells due to genetic and epigenetic instabilities, alongside remodelling of the surrounding stromal tumour microenvironment. Epithelial-specific epigenetic variations escorting this process include chromatin remodelling, histone modifications and a...

MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by suppressing mRNA translation and reducing mRNA stability. A miRNA can potentially bind many mRNAs, thereby affecting the expression of oncogenes and tumor suppressor genes as well as the activity of whole pathways. The promise of miRNA therapeutics in cancer is to harness...

INTRODUCTION • E2F1 overexpression across high-grade tumors culminates in unfavorable prognosis and chemoresistance in patients. METHODS • We integrated bioinformatics, structural and kinetic modelling, and experiments to study regulation of E2F1 by cooperative microRNAs (miRNAs) in the context of anticancer chemotherapy resistance. RESULTS • We us...

e20097 Background: Recent success with the use of checkpoint inhibition in SCLC has increased the importance of understanding the immunological tumour microenvironment. In many tumours gene expression profiling (GEP) of T-cell inflammation and IFN-gamma is correlated with response to checkpoint inhibitors. We present GEP results in a SCLC cohort an...

Motivation Extracellular vesicles (EVs), including exosomes and microvesicles, are potent and clinically valuable tools for early diagnosis, prognosis and potentially the targeted treatment of cancer. The content of EVs is closely related to the type and status of the EV-secreting cell. Circulating exosomes are a source of stable RNAs including mRN...

Myelopoiesis involves differentiation of hematopoietic stem cells to cellular populations that are restricted in their self-renewal capacity, beginning with the common myeloid progenitor (CMP) and leading to mature cells including monocytes and granulocytes. This complex process is regulated by various extracellular and intracellular signals includ...

High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach f...

Cancer is a disease of subverted regulatory pathways. In this paper, we reconstruct the regulatory network around E2F, a family of transcription factors whose deregulation has been associated to cancer progression, chemoresistance, invasiveness, and metastasis. We integrate gene expression profiles of cancer cell lines from two E2F1-driven highly a...

Background While intron retention (IR) is now widely accepted as an important mechanism of mammalian gene expression control, it remains the least studied form of alternative splicing. To delineate conserved features of IR, we performed an exhaustive phylogenetic analysis in a highly purified and functionally defined cell type comprising neutrophil...

RNA sequencing has revealed a striking diversity in transcriptomic complexity, to which alternative splicing is a major contributor. Intron retention (IR) is a conserved form of alternative splicing that was originally overlooked in normal mammalian physiology and development, due mostly to difficulties in its detection. IR has recently been reveal...

In this chapter we discuss computational methods for the prediction of microRNA (miRNA) targets. More specifically, we consider machine learning-based approaches and explain why these methods have been relatively unsuccessful in reducing the number of false positive predictions. Further we suggest approaches designed to improve their performance by...

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF...

Technological and methodological advances in multi-omics data generation and integration approaches help elucidate genetic features of complex biological traits and diseases such as prostate cancer. Due to its heterogeneity, the identification of key functional components involved in the regulation and progression of prostate cancer is a methodolog...

Key Points Dynamic intron retention programs exist in the murine megakaryocyte and erythroid and human erythroid lineages. Intron retention inversely correlates with expression levels of a large set of transcripts.

Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) e...

Technical advances in Next Generation Sequencing (NGS) provide a means to acquire deeper insights into cellular functions. The lack of standardized and automated methodologies poses a challenge for the analysis and interpretation of RNA sequencing data. We critically compare and evaluate state-of-the-art bioinformatics approaches and present a work...

This volume guides readers through the field of systems medicine by defining the terminology, and describing how established computational methods form bioinformatics and systems biology can be taken forward to an integrative systems medicine approach. Chapters provide an outlook on the role that systems medicine may or should play in various medic...

It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are...

There was evidence that RNAs are a functionally rich class of molecules not only since the arrival of the next-generation sequencing technology. Non-coding RNAs (ncRNA) could be the key to accelerated diagnosis and enhanced prediction of disease and therapy outcomes as well as the design of advanced therapeutic strategies to overcome yet unsatisfac...

The immune system is by definition multi-scale because it involves biochemical networks that regulate cell fates across cell boundaries, but also because immune cells communicate with each other by direct contact or through the secretion of local or systemic signals. Furthermore, tumor and immune cells communicate, and this interaction is affected...

This work is a showcase for the integration of systems biology and bioinformatics tools, algorithms and models for deciphering biological phenomena. More specifically, it integrates (i) prediction algorithms for identifying and characterizing molecular interactions, (ii) structural modelling of molecule complexes, (iii) network analysis approaches,...

Alterations in the expression of miRNAs have been extensively characterized in several cancers, including human colorectal cancer (CRC). Recent publications provide evidence for tissue-specific miRNA target recognition. Several computational methods have been developed to predict miRNA targets; however, all of these methods assume a general pattern...

Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are implicated in premature aging syndromes. Here we investigated a single nucleotide exchange (leucine to methionine) at position nt4738 in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain. Primary fibroblasts derived from the conplastic mous...

MicroRNAs (miRNA/miR) play an important role in gene regulatory networks through targeting mRNAs. They are involved in diverse biological processes such as cell proliferation, differentiation, angiogenesis, and apoptosis. Due to their pivotal effects on multiple genes and pathways, dysregulated miRNAs have been reported to be associated with differ...

Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Several approaches such as surgery, chemotherapy, radiotherapy, targeted therapy, or combinations thereof have been used to treat CRC patients. However, the fact that many patients develop a drug resistance during the course of the treatment is a major obstac...

The present study identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions of melanomas compared with primary melanomas. miR-638 enhanced the tumorigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling identified new candidate genes including TP53INP2 as miR-638 ta...

Malignant melanoma is highly lethal due to its aggressive invasive properties and metastatic dissemination. The transcription factor E2F1 is crucial for melanoma progression through poorly understood mechanisms. Here, we show that the miR-224/miR-452 cluster is significantly increased in advanced melanoma and invasive/metastatic cell lines that exp...

Systems biology is a multidisciplinary methodology in which quantitative biological experimental data are dissected using mathematical modelling and other computational and network biology tools, aiming at understanding the structure, function and dynamical regulation of biochemical networks. Systems biology will play a major role in the future mol...

MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergiz...

MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergiz...

A decade of successful results indicates that systems biology is the appropriate approach to investigate the regulation of complex biochemical networks involving transcriptional and post-transcriptional regulation. It becomes mandatory when dealing with highly interconnected biochemical networks, composed of hundreds of compounds, or when networks...

Drug resistance is a major cause of deaths from cancer. E2F1 is a transcription factor involved in cell cycle progression, apoptosis and metastasis through an intricate regulatory network, which includes other transcription factors like p73 and cancer-related microRNAs like miR-205. To investigate the emergence of drug resistance, we developed a me...

MicroRNAs (miRNAs) are involved in many regulatory pathways some of which are complex networks enriched in regulatory motifs like positive or negative feedback loops or coherent and incoherent feedforward loops. Their complexity makes the understanding of their regulation difficult and the interpretation of experimental data cumbersome. In this boo...

Over the last decade thousands of microRNAs (miRNAs) have been discovered in all kinds of taxa. The ever growing number of identified miRNA genes required ordered cataloging and annotation. This has led to the development of miRNA web resources. MiRNA web resources can be referred to either as web accessible databases (repositories) or web applicat...

This book reflects the current state of knowledge about the role of microRNAs in the formation and progression of solid tumours. The main focus lies on computational methods and their applications in combination with cutting edge experimental techniques that are used to approach all aspects of microRNA regulation in cancer. The use of high-throughp...

MicroRNAs (miRNAs) are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such...

In an "aging society", healthspan extension is most important. As in 2010, talks in this series of meetings in Rostock-Warnemünde demonstrated that aging is an apparently very complex process, where computational work is most useful for gaining insights, and to find interventions that counter aging and prevent or counteract aging-related diseases....

Resistance to anti-neoplastic agents is the major cause of therapy failure, leading to disease recurrence and metastasis. E2F1 is a strong inducer of apoptosis in response to DNA damage through its capacity to activate p53/p73 death pathways. Recent evidence, however, showed that E2F1, which is aberrantly expressed in advanced malignant melanomas t...

WEE1 kinase has been described as a major gate keeper at the G2 cell cycle checkpoint and to be involved in tumour progression in different malignant tumours. Here we analysed the expression levels of WEE1 in a series of melanoma patient samples and melanoma cell lines using immunoblotting, quantitative real-time PCR and immunohistochemistry. WEE1...

MicroRNA (miRNA) target hubs are genes that can be simultaneously targeted by a comparatively large number of miRNAs, a class of non-coding RNAs that mediate post-transcriptional gene repression. Although the details of target hub regulation remain poorly understood, recent experiments suggest that pairs of miRNAs can cooperate if their binding sit...

Cell adhesion in the normal colon is typically associated with differentiated cells, whereas in cancerous colon it is associated with advanced tumors. For advanced tumors growing evidence supports the existence of stem-like cells that have originated from transdifferentiation. Because stem cells can also be transformed in their own niche, at the ba...

Antigenic drift causes number of mutations in neuraminidase protein of H1N1 swine influenza virus. We analyzed neuraminidase mutations in H1N1 strains distributed over six continents, at both the sequence and structural level. Mutations in the nearby residues of the drug binding site play crucial role in the binding affinity of the drug with the pr...

In this paper we present and discuss a model-based approach to link miRNA translational control with cell signalling networks. MicroRNAs are small regulatory RNAs that are able to regulate the activity and the stability of specific messenger RNA and have been implicated in tumour progression due to their ability to translationally regulate critical...

Recent advancement in available experimental setups for the measurement of gene activity and the consequential high-throughput generation of expression data has made it absolutely necessary to utilize bioinformatics methods and applications in order to govern the vast amount of data. The analysis of this data implies the statistical inspection, the...

Antigenic drift is the ability of the swine influenza virus to undergo continuous and progressive changes in response to the host immune system. These changes dictate influenza vaccine updates annually to ensure inclusion of antigens of the most current strains. The identification of those peptides that stimulate T-cell responses, termed T-cell epi...

Non-coding RNAs gain more attention as their diverse roles in many cellular processes are discovered. At the same time, the need for efficient computational prediction of ncRNAs increases with the pace of sequencing technology. Existing tools are based on various approaches and techniques, but none of them provides a reliable ncRNA detector yet. Co...

A large-scale gene expression study of melanoma metastases was performed to identify genes involved in late-stage tumor progression. Overall 248 genes, out of more than 47,000 tested, are differentially expressed when comparing peripheral areas (invasion front) with central tumor areas of melanoma metastases. As determined by gene ontology analysis...

Homodimerisation is producing a protein?protein complex composed of two identical molecules. Dimerisation is a phenomenon often occurring in the regulation of biochemical systems like signal transduction pathways. We investigated whether the existence of a homodimer-activated receptor and the activation of homodimer transducers correspond to a more...

Homodimerisation is producing a protein protein complex composed of two identical molecules. Dimerisation is a phenomenon often occurring in the regulation of biochemical systems like signal transduction pathways. We investigated whether the existence of a homodimer-activated receptor and the activation of homodimer transducers correspond to a more...