Continuing our series looking at recent publications citing products from QIAGEN Bioinformatics, today we recap several fascinating papers from customers who made use of Ingenuity® Pathway Analysis™ to understand the meaning of changes in gene expression.
Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus
First author: Koshiro Inoue
In this PLoS One publication, scientists from the University of Tsukuba and other institutes in Japan used rats to understand why mild exercise shows benefits to spatial memory while intense exercise does not. Focusing on a stress biomarker, they performed microarray analysis and found that mild exercise regulated more genes. IPA reported that genes influenced by mild exercise were mostly connected to lipid metabolism and protein synthesis, while intense exercise was linked to a negative effect on hippocampal neuroadaptation.
Gene network analysis shows immune-signaling and ERK1/2 as novel genetic markers for multiple addiction phenotypes: alcohol, smoking and opioid addiction
First author: Cielito Reyes-Gibby
MD Anderson Cancer Center scientists report in this BMC Systems Biology paper a study of the genetic basis for alcohol, smoking, and opioid addiction. Using IPA, they found candidate genes as well as common pathways; for example, ERK1/2 was connected in all of the addiction networks.
Targeting of multiple oncogenic signaling pathways by Hsp90 inhibitor alone or in combination with berberine for treatment of colorectal cancer
First author: Yen-Hao Su
Published in Biochimica et Biophysica Acta – Molecular Cell Research, this paper demonstrates the use of heat shock protein 90 inhibitors to treat colorectal cancer, also finding that herbal medicine berberine can improve drug sensitivity. A separate data supplement shows results from IPA that contributed to a global molecular network of the significant genes studied.
Macrophage Gene Expression Associated with Remodeling of the Prepartum Rat Cervix: Microarray and Pathway Analyses
First author: Abigail Dobyns
Scientists from Loma Linda University School of Medicine and the University of Edinburgh describe in this PLoS One paper a study of differences in cervical physiology between pregnant and nonpregnant rats. IPA was used to determine that changes in resident macrophages indicate networks of genes that are collectively up- or down-regulated prior to birth. Associated pathways were linked to wound healing and inflammation.
Serial expression analysis of breast tumors during neoadjuvant chemotherapy reveals changes in cell cycle and immune pathways associated with recurrence and response
First authors: Mark Jesus M. Magbanua, Denise M. Wolf, Christina Yau
Scientists from the University of California, San Francisco, published in Breast Cancer Research the results of a breast cancer transcriptome study designed to elucidate response to neoadjuvant chemotherapy. Gene expression data were analyzed with IPA to map genes to pathways and gene ontology groups, revealing that poor response was linked to lower expression of cell cycle inhibitors.
(1) Characterization of a novel chicken muscle disorder through differential gene expression and pathway analysis using RNA-sequencing and (2) Messenger RNA sequencing and pathway analysis provide novel insights into the biological basis of chickens’ feed efficiency
First authors: Marie Mutryn and Nan Zhou
This pair of papers from scientists at the University of Delaware and Maple Leaf Farms are both highly accessed publications in BMC Genomics. The first uses RNA-seq to study an emerging muscle disorder seen recently in chickens. IPA was used to interpret the 1,500 genes differentially expressed between affected and unaffected chickens and resulted in new leads about the biological mechanism behind the disorder. In the second paper, RNA-seq data was generated to help explain the differences between chickens with high or low feed efficiency. The team used IPA for functional and canonical pathways, molecule activity prediction, and analysis of upstream regulators.
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Over the years, scientists around the world have been using our bioinformatics solutions in their research. We feel privileged that our applications have been assisting scientists in uncovering greater insights, landmark discoveries, and helping further the research that has a direct impact on humanity.
We are starting a new blog series to showcase some of these research papers from QIAGEN Bioinformatics customers. Here, we recap a handful of recent publications that used Ingenuity® Variant Analysis™ to help make sense of complex or hereditary disease phenotypes.
The use of whole-exome sequencing to disentangle complex phenotypes
First author: Hywel J Williams
This paper in the European Journal of Human Genetics comes from University College London’s GOSgene group, including lead author Hywel Williams, one of our featured researchers. Published in June, “The use of whole-exome sequencing to disentangle complex phenotypes” reports the identification of a causative mutation in two children with a previously uncharacterized disease marked by abnormal bronchial widening and peripheral neuropathy. The team used Ingenuity Variant Analysis to study exome sequence data, extracting the variants most likely to be causative. For more information on this paper, click here.
Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry (PLoS One)
First author: Louis Viollet
In May, a large team of scientists from institutions around the world report an ambitious effort to stratify patients with AHC, a neurological disorder associated with repeated bouts of temporary paralysis. The researchers analyzed mutations and genotype-phenotype correlations in nearly 200 patients, then used Ingenuity Variant Analysis to evaluate mutations detected in sequence data. In addition to finding novel mutations associated with the disorder, the team also determined that one known variant was linked to earlier onset and more severe symptoms, potentially offering a more accurate prognostic indicator (biomarker?) for newly diagnosed patients. You can read more about this work here.
A nonsense mutation of human XRCC4 is associated with adult‐onset progressive encephalocardiomyopathy
First author: Leonardo Bee
In the April issue of EMBO Molecular Medicine, scientists from Italy, the UK, and the US used exome sequencing to study twins with a progressive neurological syndrome; symptoms included cognitive impairment and depression, and both twins also had dilating cardiomyopathy. The publication reports the discovery of a homozygous nucleotide change affecting a protein associated with DNA repair. Ingenuity Variant Analysis was used to zero in on variants in the XRCC4 gene known to be involved in DNA repair. Using Ingenuity Variant Analysis’ Path to Phenotype™ investigators were able to link impairment of the XRCC4 gene to the subject’s observed developmental disorders. To learn more, click here.
Exome sequencing of case-unaffected-parents trios reveals recessive and de novo genetic variants in sporadic ALS
First author: Karyn Meltz Steinberg
In March, scientists from Washington University in St. Louis and the University of Sydney published this paper in Nature Scientific Reports. In it, they describe exome sequencing of 44 trios of patients with ALS and their unaffected parents. Using Ingenuity Variant Analysis as well as other analysis tools, they found a number of homozygous recessive and de novo variants that may be implicated in the disease. “This trio study indicates that rare private recessive variants could be a mechanism underlying some case of sporadic ALS, and that de novo mutations are also likely to play a part in the disease,” the authors report. Learn more about this work here.
Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients
First Author: Bai-Wei Gu
Finally, this May PLoS One publication from researchers at the Children’s Hospital of Philadelphia reports the use of induced pluripotent stem cells from patients with dyskeratosis congenita, a rare syndrome affecting bone marrow. By comparing these cell lines to ones with knocked-in wild type genes correcting the dysfunction, the scientists could analyze changes in telomere activity associated with the syndrome. The team used both Ingenuity Variant Analysis and Ingenuity Pathway Analysis (IPA) to look at mutations and gene expression data, finding decreased WNT signaling in mutant cells. Research paper is available here.
Did we miss your paper? Please contact us; we would love to feature you!
