Read about how researchers across the world are using QIAGEN Digital Insights solutions to accelerate their work in a variety of applications
Making sense of complex 'omics data, and developing the infrastructure to compile, store, search, analyze and visualize relevant information has significant challenges and may pose a burden to researchers without bioinformatics skills. Yet powerful insights derived from 'omics data help innovate, integrate and translate scientific results into impactful discoveries. Many noteworthy papers cite QIAGEN Digital Insights solutions and demonstrate how our tools help drive research insights and discoveries. These papers use QIAGEN Ingenuity Pathway Analysis (IPA), QIAGEN CLC and/or QIAGEN OmicSoft to help drive success. The QIAGEN Digital Insights portfolio encompasses a comprehensive, easy-to-use toolbox that ensures continuity in the NGS workflow. Here, we have curated a selection of just a few recent papers to offer a sense of the diversity of the research for which QIAGEN Digital Insights solutions makes a difference.
Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H
First author: Yuki Shibayama
Did you know on average pancreatic cancer patients acquire over 67 non-synonymous mutations? The team at Kagawa University used QIAGEN IPA to study the role of (pro)renin receptor [(P)RR] in causing genomic instability. Read their full paper here.
Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signaling
First author: Katerina Lawlor
Did you know cancer cells are not only good at proliferating but can also suppress other cells from growing? See how the team at Imperial College London investigates this phenomenon using QIAGEN IPA to understand how cancer cells induce quiescence in glioblastomas. Read their full paper here.
Multiparametric profiling of engineered nanomaterials: Unmasking the surface coating effect
First author: Audrey Gallud
Discover this fascinating research by scientists at the Karolinska Institutet who study the cytotoxic effects of engineered nanomaterials (ENMs). See how the team uses QIAGEN IPA to understand the mechanism behind the cytotoxic effects of ENMs and how to mitigate the risks. Read the full article here.
Innate immune training of granulopoiesis promotes anti-tumor activity
First author: Lydia Kalafati
Check out this exciting research by L. Kalafati and colleagues at TU Dresden, who try to promote the anti-tumor activity of trained neutrophils. See how the team uses QIAGEN IPA to understand the molecular mechanism behind reprogramming caused by trained immunity agonists. Read the paper here.
Liver-expressed cd302 and cr1l limit hepatitis C virus cross-species transmission to mice
First author: Richard J. P. Brown
Did you know the hepatitis C virus (HCV) affects 71 million people worldwide but only infects humans? Read how researchers at Paul Ehrlich Institute (PEI) use QIAGEN IPA and QIAGEN CLC Genomics Workbench to understand how mice are able to prevent HCV infection. Read their full paper here.
Vascular disease and thrombosis in SARS-CoV-2-infected rhesus macaques
First author: Malika Aid
Is there a connection between thrombosis and SARS-CoV-2 infection? Read how the team at Beth Israel Deaconess Medical Center uses QIAGEN IPA to understand the critical interactions between various pathways that lead to SARS-CoV-2-induced blood clotting in rhesus macaques. Read their full paper here.
Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19
First author: Benjamin Meckiff
Check out this critical coronavirus research by B. Meckiff and colleagues at the La Jolla Institute for Immunology, who study the role of CD4+ T cells in COVID-19. See how the team uses QIAGEN IPA to understand how different subsets of CD4+ T cells play a role in pathogenic immune responses to SARS-CoV-2 infection. Read the full article here.
Potentially adaptive SARS-CoV-2 mutations discovered with novel spatiotemporal and explainable AI models
First author: Michael R. Garvin
Can mutations in coronavirus spike proteins help it escape current vaccines? See how a group at Oak Ridge National Laboratory predicts mutational hotspots in the viral genome using QIAGEN CLC Genomics and AI models. Read the full article here.
Genomic evidence for reinfection with SARS-CoV-2: A case study
Co-author: Joel Sevinsky
Is SARS-COV-2 reinfection possible? Joel Sevinsky and his colleagues in the Nevada public health arena report the first SARS-Cov-2 reinfection case in the US. See how the team uses QIAGEN CLC Genomics Workbench for bioinformatics analysis of their SARS-CoV-2 samples to discover whether it was the same virus or a genetically different specimen. Read the full article here.
Two distinct immunopathological profiles in autopsy lungs of COVID-19
First author: Ronny Nienhold
Is unlocking differences in immune response the key to treating ARDS in COVID-19? Dig into this important coronavirus research from R. Nienhold and colleagues at Cantonal Hospital Baselland who study different immunopathological profiles in COVID-19 patients. See how the team uses QIAGEN CLC Genomics Workbench to understand the different immune patterns observed in post mortem COVID-19 lung tissue. See their full article here.
A mouse-adapted SARS-CoV-2 induces acute lung injury and mortality in standard laboratory mice
First author: Sarah R. Leist
Did you know coronaviruses are responsible for three epidemics in the 21st century? Great work by S. Leist and colleagues at the University of North Carolina at Chapel Hill, who created a mouse-adapted SARS-CoV-2 to understand the virus better. See how the team uses QIAGEN CLC Genomics Workbench to characterize this animal model and discover mechanisms for SARS-CoV-2 pathogenesis to test potential therapeutics. Read their full paper here.
Single-cell transcriptomics implicate novel monocyte and T cell immune dysregulation in sarcoidosis
First author: Lori Garman
Single-cell analysis improves our understanding of multimodal diseases. Don't miss this exciting cancer research by L. Garman and colleagues, who study the role of immune cells in sarcoidosis. The team uses QIAGEN IPA and QIAGEN OmicSoft DiseaseLand to identify dysregulated pathways using single-cell analysis. Read the full paper here.
Non-human primate blood–brain barrier and in vitro brain endothelium: From transcriptome to the establishment of a new model
First author: Catarina Chaves
Congratulations to the researchers at Sanofi for publishing their findings on a comparative model for the human blood-brain barrier (hBBB). See how the team uses QIAGEN IPA and QIAGEN OmicSoft Studio to investigate the transcriptome of brain capillaries from a non-human primate, and compare it to the hBBB. Read the full paper here.
Preclinical validation of therapeutic targets predicted by tensor factorization on heterogeneous graphs
First author: Saee Paliwal
Do we need better models for validating preclinical drug target candidates? How can we test these models? Read how researchers at BenevolentAI use QIAGEN OmicSoft DiseaseLand to evaluate the robustness of their computational model, Rosalind. Read the full paper here.
Get in touch with us! To request information on our QIAGEN Digital Insight solutions, contact bioinformaticssales@qiagen.com.
We’re always on the lookout for new and interesting ways in which researchers are using our solutions. Here is a quick recap of a few recent papers that included gene expression data analysis from our Ingenuity® Pathway Analysis™ (IPA) customers.
Network Topology Analysis of Post-Mortem Brain Microarrays Identifies More Alzheimer’s Related Genes and MicroRNAs and Points to Novel Routes for Fighting with the Disease
First author: Sreedevi Chandrasekaran
PLoS One recently published new findings about the battle against Alzheimer’s disease from a research team based at Virginia Commonwealth University. This study is part of a larger effort to understand neurodegenerative disorders, including Parkinson’s and Huntington’s, with the aim of identifying a unified underlying molecular mechanism for all three diseases. Using what may be the first-ever network-based approach to study Alzheimer’s, the team attempted to single out new drug targets by using IPA core analysis in one stage of gene expression to delve into the underlying cellular mechanisms and molecular factors of the disease. They looked at deregulated genes, biological processes, and the interactions between them to decipher the complexity of the condition, enabling them to identify patterns and heterogeneous datasets.
Blood Genome-Wide Transcriptional Profiles of HER2 Negative Breast Cancer Patients
First author: Ovidiu Balacescu
A Romanian research team recently reported using IPA to identify which biological processes and pathways were affected by gene expression changes in triple-negative breast cancer, which is also known as TNBC/ER−PR−HER2−. Triple-negative breast cancer is currently only treated with chemotherapy. Unlike ER+ and HER2+ tumors, it does not have a validated target therapy, which means that it typically has a poor clinical outcome as well as greater risk of recurrence and distant metastasis. The study showed that targeted immunotherapy could feasibly be used in conjunction with chemotherapy to treat triple-negative breast cancer and improve clinical outcomes.
Transcriptome Profiling of Musculus Longissimus Dorsi in Two Cattle Breeds with Different Intramuscular Fat Deposition
First author: Elke Albrecht
Agricultural genomics is a significant topic for today’s science community, and this paper in Genomics Data sheds new light on potential paths to improve meat quality. The authors discuss how gene expression provides details about the different intramuscular fat depositions — also known as marbling, which dictates quality and flavor — in two cattle breeds. The team compared transcriptomes of muscle cells in both breeds, identifying 569 differentially expressed genes in Japanese Black cattle. They then used IPA to locate a gene network that links parameters of cell morphology and maintenance with lipid metabolism.
Transcriptomic Sequencing Reveals a Set of Unique Genes Activated by Butyrate-Induced Histone Modification
First author: Cong-Jun Li
In this paper published by the NIH’s Gene Regulation and Systems Biology journal, a research team studied the role of butyrate, a mammalian nutritional element produced by bacterial fermentation of dietary fibers. Using normal bovine cells, the team used IPA to analyze genetic networks of differentially expressed genes as well as molecular processes and functions, ultimately discovering butyrate-induced differential expression of genes and unique genes, which are related to major cellular functions. This is a step toward understanding epigenomic regulation at the molecular level.
Post-weaning Blood Transcriptomic Differences between Yorkshire Pigs Divergently Selected for Residual Feed Intake
First author: Haibo Liu
In this BMC Genomics study, researchers from Iowa State University used IPA to help them understand variations of global gene expression in the blood transcriptome of two separate lines of recently-weaned pigs to potentially inform the development of predictive biomarkers for residual feed intake, or RFI — a standard measure for feed efficiency. The team found a difference between the low and high RFI classifications of pigs, potentially leading to improved feed efficiency through genetic selection.
To try Ingenuity Pathway Analysis, please request a trial. If you’re working on something interesting with a QIAGEN Bioinformatics solution, let us know … you could be featured on our blog!
TRANSFAC is a unique knowledge-base containing published data on eukaryotic transcription factors and miRNAs, their experimentally-proven binding sites, and regulated genes. Here we've identified a few papers referencing the use of TRANSFAC.
The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts
Shore et al.
Following up on their previously published GWAS study which looked at genetic signatures of handedness in individuals with dyslexia, the authors performed a detailed analysis of the PCSK6 locus and specifically SNP rs11855145. TRANSFAC was used for in silico analysis of transcription factor binding at this site, predicting an allelic effect on binding of several HOX transcription factors which have been shown to be involved in anterior/posterior developmental patterning. In vitro EMSA confirmed an allelic difference for transcription factor binding site affinity.
Erosion of conserved binding sites in personal genomes points to medical histories
Guturu et al.
The authors of this study used matrices from TRANSFAC to perform an analysis of variants that fall within conserved predicted transcription factor binding sites and are predicted to significantly decrease transcription factor binding affinity compared to the ancestral reference nucleotide. Their work suggests that these variants, which they call conserved binding site eroding loci (CoBELs), tend to congregate near functionally related genes and influence heritable phenotypes providing new insight into disease penetrance.
Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3β-C/EBPβ pathway
Maekawa et al.
In this study, the authors sought to characterize the mechanism of regulation of Del-1, an endothelial cell-secreted anti-inflammatory protein whose expression is inversely related to IL-17 expression. Based on prior knowledge of IL-17 stimulation resulting in phosphorylation and inactivation of the transcription factor C/EBPβ, coupled with parallel knowledge that IFNγ stimulation simultaneously enhances transcriptional activity of C/EBPβ and increases Del-1 expression, the authors hypothesized that C/EBPβ may in fact be a regulator of Del-1 expression. Promoter analysis of the Del-1 encoding gene (EDIL3) using TRANSFAC identified two predicted binding sites for C/EBPβ. The relevance of these binding sites was confirmed using ChIP-seq data provided within TRANSFAC suggesting that C/EBPβ is indeed a positive regulator of Del-1 expression.
A novel, dynamic pattern-based analysis of NF-κB binding during the priming phase of liver regeneration reveals switch-like functional regulation of target genes
Cook et al.
The authors of this study sought to characterize the role of transcriptional regulation by NF-κB during liver regeneration. They used ChIP-chip analysis to isolate NF-κB binding sites, followed by de novo motif discovery to identify other transcription factors associated with transcriptional regulation during this process. TRANSFAC was used to analyze the de novo motifs, identifying potential co-regulators including AP-1, AP-2, SMAD3, TAL1 and more. Validation of NF-κB targets was performed by ChIP qPCR with primers designed using TRANSFAC.
Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity
Herpers et al.
The aim of this study was to better understand Nrf2 and NF-κB signaling in the context of response to drug-induced liver injury. Common sources for protein-protein interaction data were used to assemble the list of genes involved in these two pathways. TRANSFAC was used to uniquely provide the set of genes bound by the terminal NFE2L2 and RELA transcription factors at the end of the respective signaling cascades. The resulting list of genes was analyzed for differential expression upon exposure to compounds associated with drug-induced liver injury.
Read more about TRANSFAC
We launched the Regulator Effects in Ingenuity Pathway Analysis (IPA) last year, and it’s been so gratifying to see how helpful this new feature has been for users of the application. It integrates results from our Upstream Regulator and Downstream Effects tools, creating hypotheses to explain what’s going on upstream that may be causing a phenotype or other functional outcome. With Regulator Effects, IPA users can identify potential mechanisms behind a phenotype, identify drug targets, and determine the biological impact of upstream molecules according to the genes they regulate.
Already, a number of publications have described interpretation advances based on Regulator Effects. Below you can find a short description of two of these articles. If you'd like to learn more about IPA, you can sign up for our webinars here.
CEMP1 Induces Transformation in Human Gingival Fibroblasts
First author: Mercedes Bermúdez
In this PLoS One paper, scientists from Mexico and the U.S. investigated the potential of CEMP1, an important regulator in tooth formation, for bone regeneration and other treatments. Starting with gene expression profiles, they found that CEMP1 modifies several genes, many of them linked to oncogenesis. “We also determined that the region spanning the CEMP1 locus is commonly amplified in a variety of cancers, and finally we found significant overexpression of CEMP1 in leukemia, cervix, breast, prostate and lung cancer,” the authors report. “Our findings suggest that CEMP1 exerts modulation of a number of cellular genes, cellular development, cellular growth, cell death, and cell cycle, and molecules associated with cancer.” The scientists note that further study is needed to determine whether CEMP1 is a novel oncogene or simply a passenger linked to another driver gene.
The team used IPA to analyze the genes identified by gene expression analysis. With Upstream Regulator Analysis, they were able to identify two potential upstream regulators: a beta-catenin protein involved in the Wnt signaling pathway, and a transcription factor known to mediate apoptosis and cell proliferation.
Inhibiting the Mammalian Target of Rapamycin Blocks the Development of Experimental Cerebral Malaria
First author: Emile Gordon
Scientists from the National Institute of Allergy and Infectious Diseases published in mBio their findings from studying a mouse model of cerebral malaria. They tested rapamycin, an mTOR inhibitor, and determined that outcomes improved significantly when treated with the medication within four days of infection. “Treatment with rapamycin increased survival, blocked breakdown of the blood-brain barrier and brain hemorrhaging, decreased the influx of both CD4+ and CD8+ T cells into the brain and the accumulation of parasitized red blood cells in the brain,” the team reports.
They analyzed transcriptional patterns caused by rapamycin to understand its effect, which suggested that leukocyte activity in the brain was blocked by the medication. “Remarkably, animals were protected against cerebral malaria even though rapamycin treatment significantly increased the inflammatory response induced by infection in both the brain and spleen,” the scientists note.
The team used IPA to identify enriched pathways, characterize networks, and predict upstream regulator effects for the differentially expressed genes they found in a comparison of untreated to treated mice. Regulator Effects features allowed the scientists to predict networks interrupted by rapamycin, identifying cellular invasion and lymphocyte proliferation, among others, as key functions inhibited by the treatment.
HGMD®, the Human Gene Mutation Database is used by scientists around the world to find information on reported genetic mutations. The papers below use the database to advance our understanding of disease, DNA dynamics, and more.
Local DNA dynamics shape mutational patterns of mononucleotide repeats in human genomes
First author: Albino Bacolla
Scientists in the US and UK published results in Nucleic Acids Research of a detailed analysis of single-base substitutions and indels in the human genome. Their findings show that certain base positions are more susceptible to mutagenesis than others. They used HGMD Professional to find mutations in specific genomic regions for analysis; the paper includes charts showing mutation patterns, germline SNPs, and more from HGMD data.
High prevalence of CDH23 mutations in patients with congenital high-frequency sporadic or recessively inherited hearing loss
First author: Kunio Mizutari
This Orphanet Journal of Rare Diseases paper from scientists in Japan sequenced 72 patients with unexplained hearing loss, finding several CDH23 mutations, some of which were novel. Mutations in the gene have been linked to Usher syndrome and other forms of hereditary hearing loss. The scientists used HGMD to find all known CDH23 mutations within nearly 70 coding regions.
Mutation analyses and prenatal diagnosis in families of X-linked severe combined immunodeficiency caused by IL2Rγ gene novel mutation
First author: Q.L. Bai
In Genetics and Molecular Research, scientists report the utility of mutation analysis of the interleukin-2 receptor gamma gene to assess carrier status and perform prenatal diagnosis for X-linked severe combined immunodeficiency. They studied two high-risk families, along with 100 controls, to evaluate the approach. Sequence variation was determined using HGMD Professional and an X-SCID database, and a new mutation was discovered in the project.
Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson’s disease
First author: Tomoko Oeda
Researchers from three hospitals in Japan published this Neurobiology of Aging report that may help stratify Parkinson’s disease patients by prognosis. They sequenced mutations in the GBA gene in 215 patients, finding that those who had mutations associated with Gaucher disease suffered dementia and psychosis much earlier than those who didn’t. The team found previously reported GBA mutations using HGMD Professional.
Comprehensive Genetic Characterization of a Spanish Brugada Syndrome Cohort
First author: Elisabet Selga
In this PLoS One publication, scientists from a number of institutions in Spain examined genetic variation among patients with Brugada syndrome, a rare genetic cardiac arrhythmia. They sequenced 14 genes in 55 patients, identifying 61 variants and finding the subset that appear pathogenic. Variants were filtered against a number of databases, including HGMD.
Learn more about HGMD.
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Many great papers citing CLC Genomics Workbench have come out just in the last few months. To give you an overview of how our software can be used in different types of research, we've selected a handful of papers to be presented here.
Illumina Synthetic Long Read Sequencing Allows Recovery of Missing Sequences even in the “Finished” C. elegans Genome
First author: Runsheng Li
This Nature Scientific Reports paper from scientists at Hong Kong Baptist University and Illumina describes an effort to analyze the C. elegans genome using synthetic long reads, recovering some missing sequence with the new assembly. Researchers used CLC Genomics Workbench to map reads to a reference genome and to analyze differences between the two assemblies.
Generation of whole genome sequences of new Cryptosporidium hominis and Cryptosporidium parvumisolates directly from stool samples
First authors: Stephen Hadfield, Justin Pachebat, Martin Swain
In this BMC Genomics publication, scientists from Singleton Hospital and Aberystwyth University in the UK report a new method for sequencing the whole genome of Cryptosporidium species from human stool samples. This approach is significantly faster and less resource-intensive than current methods to sequence this organism. CLC Genomics Workbench was used to perform bioinformatics analysis and de novo contig assembly.
Are Shiga toxin negative Escherichia coli O157:H7 enteropathogenic or enterohaemorrhagic Escherichia coli? A comprehensive molecular analysis using whole genome sequencing
First author: Mithila Ferdous
Scientists from the University of Groningen and other organizations report in the Journal of Clinical Microbiology a project designed to analyze virulence in E. coli isolates, both with and without the gene encoding Shiga toxin. They used CLC Genomics Workbench to perform de novo assembly of the sequence data.
Bioinformatic Challenges in Clinical Diagnostic Application of Targeted Next Generation Sequencing: Experience from Pheochromocytoma
First author: Joakim Crona
In PLoS One, researchers from Uppsala University and the University of Duisburg-Essen evaluated CLC Genomics Workbench and other bioinformatics tools to assess their reliability for potential use in a clinical setting. They report findings on sensitivity, specificity, read alignment, and more, reporting that these methods were at least as good as Sanger sequencing with earlier analysis tools.
Analysis of conglutin seed storage proteins across lupin species using transcriptomic, protein and comparative genomic approaches
First author: Rhonda Foley
Researchers from CSIRO Agriculture Flagship and the University of Western Australia report in BMC Plant Biology the genomic and transcriptomic analysis of conglutin proteins in lupin seeds during varying stages of development. These proteins are particularly interesting for their nutritional and pharmaceutical benefits. The authors used CLC Genomics Workbench to identify and align conglutin sequences from RNA-seq data.
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