Fios clients often feature the bioinformatics analysis we have performed for them in their publications. The following publications are the outcome of our team and co-founders’ collaboration with clients from pharmaceutical, biotechnological companies and research organisations.

You can find our publications sorted by Research Area, Research Stage, and Data Type.

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By Research Area

Microarray profiling predicts early neurological and immune phenotypic traits in advance of CNS disease

2021 – Paul Montague, Barbara Bradley, Jean Rodgers, Peter G. E. Kennedy

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. We hypothesised that recent findings of neurological features and parasite brain infiltration occurring at much earlier stages in HAT than previously thought could be explained by early activation of host genetic programmes controlling CNS disease.

Read more

Central nervous system regeneration is driven by microglia necroptosis and repopulation

2019 – Amy F. Lloyd, Claire L. Davies, Rebecca K. Holloway, et al.

This study shows our collaboration with the Medical Research Council Centre for Reproductive Health, The Queen’s Medical Research Institute, The University of Edinburgh as well as other collaborators.

Failed regeneration of CNS myelin contributes to clinical decline in neuroinflammatory and neurodegenerative diseases, for which there is an unmet therapeutic need. Impaired microglia death and/or repopulation may underpin dysregulated microglia activation in neurological diseases, and therapeutic targets to promote white matter regeneration were revealed.

Read more

Microbe-host interplay in atopic dermatitis and psoriasis

2019 – Nanna Fyhrquist, Gareth Muirhead, Stefanie Prast-Nielsen, et al.

This study shows our collaboration with several organisations for the MAARS FP7 project.

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis.

Read more

Differential sensitivity of mucosal organs to transient exposure to hydrogen sulphide in post-smolt Atlantic salmon (Salmo salar)

2023 – Carlo Lazado, Hanna Ross D. Alipio, Julie Hansen Bergstedt

The study demonstrates the physiological consequences of transient exposure of post-smolt Atlantic salmon to H2S. The fish were exposed to one of three levels of H2S for 1 h: 0 μM (unexposed), 0.6 μM (low exposure), and 1.2 μM (high exposure). Fish were allowed to recover for 24 hours and then sampled for gene expression, histology, and metabolomics analyses. Molecular profiling was performed on a subset of genes with known functions in sulphide detoxification, mucins, immunity, and stress responses, which focused on the gills, olfactory organ, skin, and distal gut.

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Genome-wide analysis clarifies the population genetic structure of wild Gilthead Sea Bream (Sparus aurata)

2021 – Francesco Maroso, Konstantinos Gkagkavouzis, Sabina De Innocentiis, et al.

The study below shows our collaboration with the Aquatrace Consortium.

Gilthead sea bream is an important target for both recreational and commercial fishing in Europe, where it is also one of the most important cultured fish. These results are of fundamental importance for the development of proper management of this species in the wild and are a first step toward the study of the potential genetic impact of the sea bream aquaculture industry.
(Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

Consequences of continuous ozonation on the health and welfare of Atlantic salmon post-smolts in a brackish water recirculating aquaculture system

2021 – Lazado Carlo, Kevin T. Stiller, Britt-Kristin Megård Reiten, João Osório, Jelena Kolarevic, Lill-Heidi Johansen

This study investigated the biological consequences of 45-day continuous ozonation on Atlantic salmon (Salmo salar) post-smolts in a brackish water recirculating aquaculture system (RAS). Microarray analysis revealed that the gills and liver were more responsive to the oxidant than the skin, with the gills being the most sensitive. Moreover, the magnitude of the transcriptomic modifications depended on the exposure duration. A functional analysis showed that genes involved in immunity and ribosomal functions were significantly affected in the gills. In contrast, genes crucial for the oxidation-reduction process were mainly targeted in the liver.

Read more

Multiomics Provide Insights into the Key Molecules and Pathways Involved in the Physiological Adaptation of Atlantic Salmon (Salmo salar) to Chemotherapeutic-Induced Oxidative Stress

2021 – Lazado C., Timmerhaus G., Breiland M., Pittman K., Hytterød S.

In this study, multiomics analysis helped understanding how a chemical oxidative stressor alters salmon physiology at both the systemic and mucosal levels. This knowledge will be pivotal in developing an evidence-driven approach to the use of oxidative therapeutics in fish, with some of the molecules and pathways identified as potential biomarkers and targets for assessing the physiological cost of these treatments.

Read more

Sonic hedgehog specifies flight feather positional information in avian wings

2020 – Lara Busby, Cristina Aceituno, Caitlin McQueen, et al.

The study below shows our collaboration with The University of Sheffield.

Classical tissue recombination experiments performed in the chick embryo provide evidence that signals operating during early limb development specify the position and identity of feathers. Sonic hedgehog (Shh) signalling in the embryonic chick wing bud specifies positional information required for the formation of adult flight feathers in a defined spatial and temporal sequence that reflects their different identities.

Read more

Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis

2023 – Jan Hilpert, Esther Groettrup-Wolfers, Hristiyan Kosturski, Laura Bennett, Catriona L K Barnes, et al.

This manuscript reports the results of a clinical trial (AKRENDO1) assessing the effects of BAY1128688 in adult premenopausal women with endometriosis-related pain symptoms over a 12-week treatment period.

Read more

Variability in the Response against Teladorsagia circumcincta in Lambs of Two Canarian Sheep Breeds

2022 –    Pérez-Hernández T.,  Hernández J., Machín C., McNeilly T. , Nisbet A. et al.

The increasing resistance to anthelmintics has necessitated the exploration of alternative control strategies of gastrointestinal nematode (GIN) infections. A sustainable option is genetic selection based on differences in susceptibility to GIN infection between and within breeds of sheep. Here, three-month-old Canaria Hair breed (GIN-resistant) and Canaria Sheep breed (GIN-susceptible) showed no significant between-breed differences after trickle infection with Teladorsagia circumcincta, whereas considerable individual variability was found in both breeds. Next, data from lambs of both breeds were used to explore the relationships between parasitological variables and T. circumcincta-specific IgA levels, local immune cell populations, and abomasal lymph node gene expression to understand the possible mechanisms underlying resistance. Mucosal IgA levels as well as numbers of globular leukocytes and MHC-II+ cells were associated with protection. Analysis of lymph node gene expression revealed the associations between lower parasite numbers and cumulative fecal egg counts and several immune pathways, such as leukocyte cell adhesion, activation and differentiation of T cells, in particular CD4+ and IL-4 production. The data obtained here may inform on the relationship between phenotypic resistance variability and protective responses at the humoral, cellular, and transcriptomic levels, thus contributing to identifying immune responses in young lambs that could be used as markers for selection.
(Just one of several genomics publications featuring bioinformatics research from Fios Genomics).

Read more

Structural and functional annotation of the porcine immunome

2013 – Dawson, H.D., Loveland, J.E., Pascal, G., et al.

The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes,  3,472 transcripts were annotated. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. Gene duplications for 18 genes were found, including 13 immune response genes and five non-immune response genes discovered in the annotation process.

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Exploring the transcriptomic changes underlying recombinant vaccine efficacy against Teladorsagia circumcincta in 3-month-old lambs

2023 – Tara Pérez-Hernández, Julia N. Hernández, Stewart T.G. Burgess, et al.

Teladorsagia circumcincta is an abomasal parasitic nematode that can cause serious issues in small ruminant production, which are aggravated by drug resistance. Vaccines have been suggested as a feasible, long-lasting alternative for control since adaptation to the host’s immune mechanisms by helminths develops at a much slower pace than anthelmintic resistance. Recently, a T. circumcincta recombinant subunit vaccine yielded over a 60% reduction in egg excretion and worm burden and induced strong humoral and cellular anti-helminth responses in vaccinated 3-month-old Canaria Hair Breed (CHB) lambs, but Canaria Sheep (CS) of a similar age were not protected by the vaccine. Here, we compared the transcriptomic profiles in the abomasal lymph nodes of such 3-month-old CHB and CS vaccinates 40 days after infection with T. circumcincta to understand differences in responsiveness at the molecular level.

Read more

Structural and functional annotation of the porcine immunome

2013 – Dawson, H.D., Loveland, J.E., Pascal, G., et al.

The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, 3,472 transcripts were annotated. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. Gene duplications for 18 genes were found, including 13 immune response genes and five non-immune response genes discovered in the annotation process.
(Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

Ritonavir reverses resistance to docetaxel and cabazitaxel in prostate cancer cells with acquired resistance to docetaxel 

2024 – Eric van der Putten, Katja Wosikowski, Jos H.Beijnen, et al.

This study investigates the mechanisms of acquired resistance to docetaxel in prostate cancer cells, focusing on the role of P-glycoprotein (P-gp) drug transporters.

Read more

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

2023 – Melanie M. Frigault, Arushi Mithal, Harvey Wong, et al.

This study investigates the pharmacodynamic (PD) effect of CDK9 inhibition in preclinical models and in blood samples from patients (DH-DLBCL [n=10] and MYC+ NHL [n=5]) treated with 30 mg i.v. QW enitociclib.

Read more

The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia

2023 – Issa, G.C., Aldoss, I., DiPersio, J, et al.

This study shows our collaboration with Syndax Pharmaceuticals.

Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin–KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399).

Read more

Anti-cancer activity of ST101, a novel antagonist of CCAAT/enhancer binding protein β

2022 – Emma Darvishi, Lila Ghamsari, Siok F. Leong, Ricardo Ramirez, Jim A. Rotolo, et al.

This study shows our collaboration with Sapience Therapeutics.

CCAAT/Enhancer Binding Protein β (C/EBPβ) is a basic leucine zipper (bZIP) family transcription factor that is upregulated or overactivated in many cancers, resulting in gene transactivation that drives oncogenesis. C/EBPβ dimerization regulates binding to DNA at the canonical TTGCGCAA motif and subsequent transcriptional activity, suggesting that disruption of dimerization represents a powerful approach to inhibit this previously ‘undruggable’ oncogenic target. Here we describe the mechanism of action and anti-tumor activity of ST101, a novel and selective peptide antagonist of C/EBPβ that is currently in clinical evaluation in patients with advanced solid tumors.

Read more

Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma

2021 – Thomas Powles, Toni K. Choueiri, Robert J. Motzer, Eric Jonasch, et al.

This study shows our collaboration with several organisations including Queen Mary University of London, Memorial Sloan Kettering Cancer Center, University of Texas

In this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analysed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analysed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods.

Read more

ctDNA guiding adjuvant immunotherapy in urothelial carcinoma

2021 – Thomas Powles, Zoe June Assaf, et al.

This study shows our collaboration with Genentech.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse. This study evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer.

Read more

Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma

2020 – Robin Kate Kelley, Tim Meyer, Lorenza Rimassa, et al.

This study shows our collaboration with Exelixis.

The phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes.

Read more

CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy

2020 – Anne Lai, Jessica Sorrentino, Konstantin Dragnev, et al.

This study shows our collaboration with G1 Therapeutics.

Combination treatment with chemotherapy and immune checkpoint inhibitors (ICIs) has demonstrated meaningful clinical benefit to patients. Transient CDK4/6 inhibition by trilaciclib was sufficient to enhance and prolong the duration of the antitumor response by chemotherapy/ICI combinations, suggesting a role for the transient cell cycle arrest of tumor immune infiltrates in remodeling the tumor microenvironment.

Read more

Development of a gene expression–based prognostic signature for IDH wild-type glioblastoma

2020 – Radia M. Johnson, Heidi S. Phillips, Carlos Bais, et al.

This study shows our collaboration with Genentech.

We aimed to develop a gene expression–based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of glioblastoma clinical trial populations.

Read more

Comprehensive Profiling of Poor-Risk Paired Primary and Recurrent Triple-Negative Breast Cancers Reveals Immune Phenotype Shifts

2020 – Katherine E. Hutchinson, Susan E. Yost, Ching-Wei Chang, et al.

This study shows our collaboration with Genentech.

Emerging data suggest immune checkpoint inhibitors have reduced efficacy in heavily pretreated triple-negative breast cancers (TNBC), but underlying mechanisms are poorly understood. To better understand the phenotypic evolution of TNBCs, we studied the genomic and transcriptomic profiles of paired tumors from patients with TNBC.
(Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer

2020 – Marie-Claire Wagle, Joseph Castillo, Shrividhya Srinivasan, et al.

This study shows our collaboration with Genentech.

Prostate cancer is the second leading cause of cancer-related death in men. Our findings suggest that high tumor fusion burden may be a more appropriate biomarker than tumor mutational burden in prostate cancer, as it more closely associates with immunogenicity, and suggests that tumors with high fusion burden could be potential candidates for immunotherapeutic agents.

Read more

Application of pharmacogenomics and bioinformatics to exemplify the utility of human ex vivo organoculture models in the field of precision medicine

2019 – Karen Cowan, Graeme Macluskie, Michael Finch, et al.

This study shows our collaboration with REPROCELL.

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines.
(Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea

2022 – Emma C Johns, Daniel L Halligan, Triin Tammsalu, et al.

This study shows our collaboration with Queen’s Medical Research Institute.

Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised. 3′ mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9) were performed.

Read more

Discovery through Machine Learning and Preclinical Validation of Novel Anti-Diabetic Peptides

2021 – Rory Casey, Alessandro Adelfio, Martin Connolly, Audrey Wall, Ian Holyer and Nora Khaldi 

This study shows our collaboration with Nuritas Ltd.

Using machine learning, we present novel anti-diabetic peptides which are less than 16 amino acids in length, distinct from human signalling peptides. We validate the capacity of these peptides to stimulate glucose uptake and Glucose transporter type 4 (GLUT4) translocation in vitro. In obese insulin-resistant mice, predicted peptides significantly lower plasma glucose, reduce glycated haemoglobin and even improve hepatic steatosis when compared to treatments currently in use in a clinical setting.

Read more

By Research Stage

Integration of genomic and transcriptomic data of inbred mouse models for polygenic obesity and leanness revealed “obese” and “lean” candidate alleles in polyadenylation signals

2024 – Martin Simon, Špela Mikec, Nicholas M. Morton, et al.

This study investigates the association between genetic variations in polyadenylation signals (PAS-SNPs) and obesity in inbred mouse models.

Read more

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

2023 – Melanie M. Frigault, Arushi Mithal, Harvey Wong, et al.

This study investigates the pharmacodynamic (PD) effect of CDK9 inhibition in preclinical models and in blood samples from patients (DH-DLBCL [n=10] and MYC+ NHL [n=5]) treated with 30 mg i.v. QW enitociclib.

Read more

Microarray profiling predicts early neurological and immune phenotypic traits in advance of CNS disease

2021 – Paul Montague, Barbara Bradley, Jean Rodgers, Peter G. E. Kennedy

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. We hypothesised that recent findings of neurological features and parasite brain infiltration occurring at much earlier stages in HAT than previously thought could be explained by early activation of host genetic programmes controlling CNS disease.

Read more

Multiomics Provide Insights into the Key Molecules and Pathways Involved in the Physiological Adaptation of Atlantic Salmon (Salmo salar) to Chemotherapeutic-Induced Oxidative Stress

2021 – Lazado C., Timmerhaus G., Breiland M., Pittman K., Hytterød S.

In this study, multiomics analysis helped understanding how a chemical oxidative stressor alters salmon physiology at both the systemic and mucosal levels. This knowledge will be pivotal in developing an evidence-driven approach to the use of oxidative therapeutics in fish, with some of the molecules and pathways identified as potential biomarkers and targets for assessing the physiological cost of these treatments.

Read more

Consequences of continuous ozonation on the health and welfare of Atlantic salmon post-smolts in a brackish water recirculating aquaculture system

2021 – Lazado Carlo, Kevin T.Stiller, Britt-Kristin Megård Reiten, João Osório, Jelena Kolarevic, Lill-Heidi Johansen

This study investigated the biological consequences of 45-day continuous ozonation on Atlantic salmon (Salmo salar) post-smolts in a brackish water recirculating aquaculture system (RAS). Microarray analysis revealed that the gills and liver were more responsive to the oxidant than the skin, with the gills being the most sensitive. Moreover, the magnitude of the transcriptomic modifications depended on the exposure duration. A functional analysis showed that genes involved in immunity and ribosomal functions were significantly affected in the gills. In contrast, genes crucial for the oxidation-reduction process were mainly targeted in the liver.

Read more

Discovery through Machine Learning and Preclinical Validation of Novel Anti-Diabetic Peptides

2021 – Rory Casey, Alessandro Adelfio, Martin Connolly, Audrey Wall, Ian Holyer and Nora Khaldi 

This study shows our collaboration with Nuritas Ltd.

Using machine learning, we present novel anti-diabetic peptides which are less than 16 amino acids in length, distinct from human signalling peptides. We validate the capacity of these peptides to stimulate glucose uptake and Glucose transporter type 4 (GLUT4) translocation in vitro. In obese insulin-resistant mice, predicted peptides significantly lower plasma glucose, reduce glycated haemoglobin and even improve hepatic steatosis when compared to treatments currently in use in a clinical setting.

Read more

Central nervous system regeneration is driven by microglia necroptosis and repopulation

2019 – Amy F. Lloyd, Claire L. Davies, Rebecca K. Holloway, et al.

This study shows our collaboration with the Medical Research Council Centre for Reproductive Health, The Queen’s Medical Research Institute, The University of Edinburgh as well as other collaborators.

Failed regeneration of CNS myelin contributes to clinical decline in neuroinflammatory and neurodegenerative diseases, for which there is an unmet therapeutic need. Impaired microglia death and/or repopulation may underpin dysregulated microglia activation in neurological diseases, and therapeutic targets to promote white matter regeneration were revealed.

Read more

Genetics of vegetarianism: A genome-wide association study

2023 – Nabeel R. Yaseen, Catriona L.K. Barnes, Lingwei Sun, et al.

In this study, a genome-wide association study (GWAS) was used to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, one SNP on chromosome 18 that is associated with vegetarianism at the genome-wide significant level (rs72884519, β = -0.11, P = 4.997 x 10−8) was identified, along with an additional 201 suggestively significant variants.

Read more

Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis

2023 – Jan Hilpert, Esther Groettrup-Wolfers, Hristiyan Kosturski, Laura Bennett, Catriona L K Barnes, et al.

This manuscript reports the results of a clinical trial (AKRENDO1) assessing the effects of BAY1128688 in adult premenopausal women with endometriosis-related pain symptoms over a 12-week treatment period.

Read more

Defects in sperm capacitation/fertilizing ability are equally prevalent across ages in men seeking fertility assistance

2023 – Fady I. Sharara, G. Charles Ostemeier and Alexander J. Travis

This study shows our collaboration with Androvia LifeSciences.

The aim of this study was to determine how capacitation ability, measured by Cap-Score™, and traditional semen analysis measures (volume, concentration, motility) changes with age in men questioning their fertility (MQF).

Read more

Anti-cancer activity of ST101, a novel antagonist of CCAAT/enhancer binding protein β

2022 – Emma Darvishi, Lila Ghamsari, Siok F. Leong, Ricardo Ramirez, Jim A. Rotolo, et al.

This study shows our collaboration with Sapience Therapeutics.

CCAAT/Enhancer Binding Protein β (C/EBPβ) is a basic leucine zipper (bZIP) family transcription factor that is upregulated or overactivated in many cancers, resulting in gene transactivation that drives oncogenesis. C/EBPβ dimerization regulates binding to DNA at the canonical TTGCGCAA motif and subsequent transcriptional activity, suggesting that disruption of dimerization represents a powerful approach to inhibit this previously ‘undruggable’ oncogenic target. Here we describe the mechanism of action and anti-tumor activity of ST101, a novel and selective peptide antagonist of C/EBPβ that is currently in clinical evaluation in patients with advanced solid tumors.

Read more

Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea

2022 – Emma C Johns, Daniel L Halligan, Triin Tammsalu, et al.

This study shows our collaboration with Queen’s Medical Research Institute.

Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised. 3′ mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9) were performed.

Read more

ctDNA guiding adjuvant immunotherapy in urothelial carcinoma

2021 – Thomas Powles, Zoe June Assaf, et al.

This study shows our collaboration with Genentech.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse. This study evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer.

Read more

Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma

2020 – Robin Kate Kelley, Tim Meyer, Lorenza Rimassa, et al.

This study shows our collaboration with Exelixis.

The phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes.

Read more

CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy

2020 – Anne Lai, Jessica Sorrentino, Konstantin Dragnev, et al.

This study shows our collaboration with G1 Therapeutics.

Combination treatment with chemotherapy and immune checkpoint inhibitors (ICIs) has demonstrated meaningful clinical benefit to patients. Transient CDK4/6 inhibition by trilaciclib was sufficient to enhance and prolong the duration of the antitumor response by chemotherapy/ICI combinations, suggesting a role for the transient cell cycle arrest of tumor immune infiltrates in remodeling the tumor microenvironment.

Read more

Development of a gene expression–based prognostic signature for IDH wild-type glioblastoma

2020 – Radia M. Johnson, Heidi S. Phillips, Carlos Bais, et al.

This study shows our collaboration with Genentech.

We aimed to develop a gene expression–based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of glioblastoma clinical trial populations.

Read more

Comprehensive Profiling of Poor-Risk Paired Primary and Recurrent Triple-Negative Breast Cancers Reveals Immune Phenotype Shifts

2020 – Katherine E. Hutchinson, Susan E. Yost, Ching-Wei Chang, et al.

This study shows our collaboration with Genentech.

Emerging data suggest immune checkpoint inhibitors have reduced efficacy in heavily pretreated triple-negative breast cancers (TNBC), but underlying mechanisms are poorly understood. To better understand the phenotypic evolution of TNBCs, we studied the genomic and transcriptomic profiles of paired tumors from patients with TNBC.
(Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer

2020 – Marie-Claire Wagle, Joseph Castillo, Shrividhya Srinivasan, et al.

This study shows our collaboration with Genentech.

Prostate cancer is the second leading cause of cancer-related death in men. Our findings suggest that high tumor fusion burden may be a more appropriate biomarker than tumor mutational burden in prostate cancer, as it more closely associates with immunogenicity, and suggests that tumors with high fusion burden could be potential candidates for immunotherapeutic agents.

Read more

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

2020 – A.K. Sorial, I.M.J. Hofer, M. Tselepi, et al.

This study highlights the expertise of our team.

In cartilage, the osteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC, and with differential methylation of PLEC CpG dinucleotides, forming eQTLs and mQTLs respectively. We sought to assess whether these PLEC functional effects were cartilage specific.

Read more

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

2020 – Laura J. Smyth, Christopher C. Patterson, Elizabeth J. Swan, et al.

This study shows our collaboration with Queen’s University Belfast.

A subset of individuals with type 1 diabetes will develop diabetic kidney disease (DKD). DKD is heritable and large-scale genome-wide association studies have begun to identify genetic factors that influence DKD. Evidence confirming that methylation sites influence the development of DKD may aid risk prediction tools and stimulate research to identify epigenomic therapies which might be clinically useful for this disease.

Read more

Characterization of the xenobiotic response of Caenorhabditis elegans to the anthelmintic drug albendazole and the indentification of novel drug glucoside metabolites

2010 – Laing, S.T. et al.

This study investigated how the model nematode Caenorhabditis elegans responds to and metabolizes albendazole, one of the most important anthelmintic drugs for human and animal use. Using a mutant strain lacking the β-tubulin drug target to minimize generalized stress responses, we show that the transcriptional response is dominated by genes encoding XMEs (xenobiotic-metabolizing enzymes), particularly cytochrome P450s and UGTs (UDP-glucuronosyl transferases).

Read more

Hepatotoxicity of AKR1C3 Inhibitor BAY1128688: Findings from an Early Terminated Phase IIa Trial for the Treatment of Endometriosis

2023 – Jan Hilpert, Esther Groettrup-Wolfers, Hristiyan Kosturski, Laura Bennett, Catriona L K Barnes, et al.

This manuscript reports the results of a clinical trial (AKRENDO1) assessing the effects of BAY1128688 in adult premenopausal women with endometriosis-related pain symptoms over a 12-week treatment period.

Read more

Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib vs everolimus in advanced renal cell carcinoma

2021 – Thomas Powles, Toni K. Choueiri, Robert J. Motzer, Eric Jonasch, et al.

This study shows our collaboration several organisations including Queen Mary University of London, Memorial Sloan Kettering Cancer Center, University of Texas

In this exploratory analysis, plasma biomarkers from baseline and week 4 from 621 of 658 randomized patients were analyzed for CA9, HGF, MET, GAS6, AXL, VEGF, VEGFR2, and IL-8. PFS and OS were analyzed by baseline biomarker levels as both dichotomized and continuous variables using univariate and multivariable methods.

Read more

Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer

2020 – Marie-Claire Wagle, Joseph Castillo, Shrividhya Srinivasan, et al.

This study shows our collaboration with Genentech.

Prostate cancer is the second leading cause of cancer-related death in men. Our findings suggest that high tumor fusion burden may be a more appropriate biomarker than tumor mutational burden in prostate cancer, as it more closely associates with immunogenicity, and suggests that tumors with high fusion burden could be potential candidates for immunotherapeutic agents.

Read more

Application of pharmacogenomics and bioinformatics to exemplify the utility of human ex vivo organoculture models in the field of precision medicine

2019 – Karen Cowan, Graeme Macluskie, Michael Finch, et al.

This study shows our collaboration with REPROCELL.

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. (Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

Microbe-host interplay in atopic dermatitis and psoriasis

2019 – Nanna Fyhrquist, Gareth Muirhead, Stefanie Prast-Nielsen, et al.

This study shows our collaboration with several organisations for the MAARS FP7 project

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis.

Read more

By Data Type

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

2020 – A.K. Sorial, I.M.J. Hofer, M. Tselepi, et al.

This study highlights the expertise of our team.

In cartilage, the osteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC, and with differential methylation of PLEC CpG dinucleotides, forming eQTLs and mQTLs respectively. We sought to assess whether these PLEC functional effects were cartilage specific.

Read more

Functional testing of thousands of osteoarthritis-associated variants for regulatory activity

2019 – Jason C. Klein, Aidan Keith, Sarah J. Rice, et al.

This study highlights the expertise of our team.

To date, genome-wide association studies have implicated at least 35 loci in osteoarthritis but, due to linkage disequilibrium, the specific variants underlying these associations and the mechanisms by which they contribute to disease risk have yet to be pinpointed. This study provides a framework for prioritization of GWAS variants and highlights a role of HBP1 and Wnt signaling in osteoarthritis pathogenesis.

Read more

Genetics of vegetarianism: A genome-wide association study

2023 – Nabeel R. Yaseen, Catriona L.K. Barnes, Lingwei Sun, et al.

In this study, a genome-wide association study (GWAS) was used to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, one SNP on chromosome 18 that is associated with vegetarianism at the genome-wide significant level (rs72884519, β = -0.11, P = 4.997 x 10−8) was identified, along with an additional 201 suggestively significant variants.

Read more

Development of a gene expression–based prognostic signature for IDH wild-type glioblastoma

2020 – Radia M. Johnson, Heidi S. Phillips, Carlos Bais, et al.

This study shows our collaboration with Genentech.

We aimed to develop a gene expression–based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of glioblastoma clinical trial populations.

Read more

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

2020 – Laura J. Smyth, Christopher C. Patterson, Elizabeth J. Swan, et al.

This study shows our collaboration with Queen’s University Belfast.

A subset of individuals with type 1 diabetes will develop diabetic kidney disease (DKD). DKD is heritable and large-scale genome-wide association studies have begun to identify genetic factors that influence DKD. Evidence confirming that methylation sites influence the development of DKD may aid risk prediction tools and stimulate research to identify epigenomic therapies which might be clinically useful for this disease.

Read more

Application of pharmacogenomics and bioinformatics to exemplify the utility of human ex vivo organoculture models in the field of precision medicine

2019 – Karen Cowan, Graeme Macluskie, Michael Finch, et al.

This study shows our collaboration with REPROCELL.

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. (Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

2020 – Laura J. Smyth, Christopher C. Patterson, Elizabeth J. Swan, et al.

This study shows our collaboration with Queen’s University Belfast.

A subset of individuals with type 1 diabetes will develop diabetic kidney disease (DKD). DKD is heritable and large-scale genome-wide association studies have begun to identify genetic factors that influence DKD. Evidence confirming that methylation sites influence the development of DKD may aid risk prediction tools and stimulate research to identify epigenomic therapies which might be clinically useful for this disease.

Read more

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

2020 – A.K. Sorial, I.M.J. Hofer, M. Tselepi, et al.

This study highlights the expertise of our team.

In cartilage, the osteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC, and with differential methylation of PLEC CpG dinucleotides, forming eQTLs and mQTLs respectively. We sought to assess whether these PLEC functional effects were cartilage specific.

Read more

Integration of genomic and transcriptomic data of inbred mouse models for polygenic obesity and leanness revealed “obese” and “lean” candidate alleles in polyadenylation signals

2024 – Martin Simon, Špela Mikec, Nicholas M. Morton, et al.

This study investigates the association between genetic variations in polyadenylation signals (PAS-SNPs) and obesity in inbred mouse models.

Read more

Genetics of vegetarianism: A genome-wide association study

2023 – Nabeel R. Yaseen, Catriona L.K. Barnes, Lingwei Sun, et al.

In this study, a genome-wide association study (GWAS) was used to identify loci associated with strict vegetarianism in UK Biobank participants. Comparing 5,324 strict vegetarians to 329,455 controls, one SNP on chromosome 18 that is associated with vegetarianism at the genome-wide significant level (rs72884519, β = -0.11, P = 4.997 x 10−8) was identified, along with an additional 201 suggestively significant variants.

Read more

Microarray profiling predicts early neurological and immune phenotypic traits in advance of CNS disease

2021 – Paul Montague, Barbara Bradley, Jean Rodgers, Peter G. E. Kennedy

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. We hypothesised that recent findings of neurological features and parasite brain infiltration occurring at much earlier stages in HAT than previously thought could be explained by early activation of host genetic programmes controlling CNS disease.

Read more

Discovery through Machine Learning and Preclinical Validation of Novel Anti-Diabetic Peptides

2021 – Rory Casey, Alessandro Adelfio, Martin Connolly, Audrey Wall, Ian Holyer and Nora Khaldi 

This study shows our collaboration with Nuritas Ltd

Using machine learning, we present novel anti-diabetic peptides which are less than 16 amino acids in length, distinct from human signalling peptides. We validate the capacity of these peptides to stimulate glucose uptake and Glucose transporter type 4 (GLUT4) translocation in vitro. In obese insulin-resistant mice, predicted peptides significantly lower plasma glucose, reduce glycated haemoglobin and even improve hepatic steatosis when compared to treatments currently in use in a clinical setting.

Read more

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

2020 – A.K. Sorial, I.M.J. Hofer, M. Tselepi, et al.

This study highlights the expertise of our team.

In cartilage, the osteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC, and with differential methylation of PLEC CpG dinucleotides, forming eQTLs and mQTLs respectively. We sought to assess whether these PLEC functional effects were cartilage specific.

Read more

Development of a gene expression–based prognostic signature for IDH wild-type glioblastoma

2020 – Radia M. Johnson, Heidi S. Phillips, Carlos Bais, et al.

This study shows our collaboration with Genentech.

We aimed to develop a gene expression–based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of glioblastoma clinical trial populations.

Read more

DNA Methylation Associated With Diabetic Kidney Disease in Blood-Derived DNA

2020 – Laura J. Smyth, Christopher C. Patterson, Elizabeth J. Swan, et al.

This study shows our collaboration with Queen’s University Belfast.

A subset of individuals with type 1 diabetes will develop diabetic kidney disease (DKD). DKD is heritable and large-scale genome-wide association studies have begun to identify genetic factors that influence DKD. Evidence confirming that methylation sites influence the development of DKD may aid risk prediction tools and stimulate research to identify epigenomic therapies which might be clinically useful for this disease.

Read more

Functional testing of thousands of osteoarthritis-associated variants for regulatory activity

2019 – Jason C. Klein, Aidan Keith, Sarah J. Rice, et al.

This study highlights the expertise of our team.

To date, genome-wide association studies have implicated at least 35 loci in osteoarthritis but, due to linkage disequilibrium, the specific variants underlying these associations and the mechanisms by which they contribute to disease risk have yet to be pinpointed. This study provides a framework for prioritization of GWAS variants and highlights a role of HBP1 and Wnt signalling in osteoarthritis pathogenesis.

Read more

Microarray profiling predicts early neurological and immune phenotypic traits in advance of CNS disease

2021 – Paul Montague, Barbara Bradley, Jean Rodgers, Peter G. E. Kennedy

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major cause of mortality and morbidity in sub-Saharan Africa. We hypothesised that recent findings of neurological features and parasite brain infiltration occurring at much earlier stages in HAT than previously thought could be explained by early activation of host genetic programmes controlling CNS disease.

Read more

Discovery through Machine Learning and Preclinical Validation of Novel Anti-Diabetic Peptides

2021 – Rory Casey, Alessandro Adelfio, Martin Connolly, Audrey Wall, Ian Holyer and Nora Khaldi 

This study shows our collaboration with Nuritas Ltd

Using machine learning, we present novel anti-diabetic peptides which are less than 16 amino acids in length, distinct from human signalling peptides. We validate the capacity of these peptides to stimulate glucose uptake and Glucose transporter type 4 (GLUT4) translocation in vitro. In obese insulin-resistant mice, predicted peptides significantly lower plasma glucose, reduce glycated haemoglobin and even improve hepatic steatosis when compared to treatments currently in use in a clinical setting.

Read more

Microbe-host interplay in atopic dermatitis and psoriasis

2019 – Nanna Fyhrquist, Gareth Muirhead, Stefanie Prast-Nielsen, et al.

This study shows our collaboration with several organisations for the MAARS FP7 project

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis.

Read more

Differential sensitivity of mucosal organs to transient exposure to hydrogen sulphide in post-smolt Atlantic salmon (Salmo salar)

2023 – Carlo Lazado, Hanna Ross D. Alipio, Julie Hansen Bergstedt

The study demonstrates the physiological consequences of transient exposure of post-smolt Atlantic salmon to H2S. The fish were exposed to one of three levels of H2S for 1 h: 0 μM (unexposed), 0.6 μM (low exposure), and 1.2 μM (high exposure). Fish were allowed to recover for 24 h and then sampled for gene expression, histology, and metabolomics analyses. Molecular profiling was performed on a subset of genes with known functions in sulphide detoxification, mucins, immunity, and stress responses, which focused on the gills, olfactory organ, skin, and distal gut.

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The circulating plasma metabolome of Neoparamoeba perurans-infected Atlantic salmon (Salmo salar))

2022 – Carlo C. Lazado, Mette W. Breiland, Francisco Furtado et al.

The study reports the circulating plasma metabolome of Atlantic salmon (Salmo salar) experimentally infected with Neoparamoeba perurans—the causative agent of amoebic gill disease (AGD).

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Integrated Analysis of Transcript, Protein and Metabolite Data To Study Lignin Biosynthesis in Hybrid Aspen

2009- Bylesjo M, Nilsson R et al.

In this paper, a strategy is outlined for informative data generation and integrated modeling of systematic changes in transcript, protein and metabolite profiles measured from hybrid aspen samples.

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Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

2023 – Melanie M. Frigault, Arushi Mithal, Harvey Wong, et al.

This study investigates the pharmacodynamic (PD) effect of CDK9 inhibition in preclinical models and in blood samples from patients (DH-DLBCL [n=10] and MYC+ NHL [n=5]) treated with 30 mg i.v. QW enitociclib.

Read more

Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma

2020 – Robin Kate Kelley, Tim Meyer, Lorenza Rimassa, et al.

This study shows our collaboration with Exelixis.

The phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes.

Read more

Development of a gene expression–based prognostic signature for IDH wild-type glioblastoma

2020 – Radia M. Johnson, Heidi S. Phillips, Carlos Bais, et al.

This study shows our collaboration with Genentech.

We aimed to develop a gene expression–based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of glioblastoma clinical trial populations.

Read more

Comprehensive Profiling of Poor-Risk Paired Primary and Recurrent Triple-Negative Breast Cancers Reveals Immune Phenotype Shifts

2020 – Katherine E. Hutchinson, Susan E. Yost, Ching-Wei Chang, et al.

This study shows our collaboration with Genentech.

Emerging data suggest immune checkpoint inhibitors have reduced efficacy in heavily pretreated triple-negative breast cancers (TNBC), but underlying mechanisms are poorly understood. To better understand the phenotypic evolution of TNBCs, we studied the genomic and transcriptomic profiles of paired tumors from patients with TNBC. (Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

Read more

Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin gene PLEC

2020 – A.K. Sorial, I.M.J. Hofer, M. Tselepi, et al.

This study highlights the expertise of our team.

In cartilage, the osteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression of PLEC, and with differential methylation of PLEC CpG dinucleotides, forming eQTLs and mQTLs respectively. We sought to assess whether these PLEC functional effects were cartilage specific.

Read more

Sonic hedgehog specifies flight feather positional information in avian wings

2020 – Lara Busby, Cristina Aceituno, Caitlin McQueen, et al.

The study below shows our collaboration with The University of Sheffield.

Classical tissue recombination experiments performed in the chick embryo provide evidence that signals operating during early limb development specify the position and identity of feathers. Sonic hedgehog (Shh) signalling in the embryonic chick wing bud specifies positional information required for the formation of adult flight feathers in a defined spatial and temporal sequence that reflects their different identities.

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Parallel evolution and adaptation to environmental factors in a marine flatfish: Implications for fisheries and aquaculture management of the turbot (Scophthalmus maximus)

2018 – Fernanda Dotti do Prado, Manuel Vera, Miguel Hermida, et al.

The study below shows our collaboration with the Department of Zoology, Genetics and Physical Anthropology, University of Santiago de Compostela, Lugo, Spain.

This study evaluated the genetic structure of turbot throughout its natural distribution range (672 individuals; 20 populations) by analyzing allele frequency data from 755 single nucleotide polymorphism discovered and genotyped by double-digest RAD sequencing.

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Ritonavir reverses resistance to docetaxel and cabazitaxel in prostate cancer cells with acquired resistance to docetaxel 

2024 – Eric van der Putten, Katja Wosikowski, Jos H.Beijnen, et al.

This study investigates the mechanisms of acquired resistance to docetaxel in prostate cancer cells, focusing on the role of P-glycoprotein (P-gp) drug transporters.

Read more

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

2023 – Melanie M. Frigault, Arushi Mithal, Harvey Wong, et al.

This study investigates the pharmacodynamic (PD) effect of CDK9 inhibition in preclinical models and in blood samples from patients (DH-DLBCL [n=10] and MYC+ NHL [n=5]) treated with 30 mg i.v. QW enitociclib.

Read more

Anti-cancer activity of ST101, a novel antagonist of CCAAT/enhancer binding protein β

2022 – Emma Darvishi, Lila Ghamsari, Siok F. Leong, Ricardo Ramirez, Jim A. Rotolo, et al.

This study shows our collaboration with Sapience Therapeutics.

CCAAT/Enhancer Binding Protein β (C/EBPβ) is a basic leucine zipper (bZIP) family transcription factor that is upregulated or overactivated in many cancers, resulting in gene transactivation that drives oncogenesis. C/EBPβ dimerization regulates binding to DNA at the canonical TTGCGCAA motif and subsequent transcriptional activity, suggesting that disruption of dimerization represents a powerful approach to inhibit this previously ‘undruggable’ oncogenic target. Here we describe the mechanism of action and anti-tumor activity of ST101, a novel and selective peptide antagonist of C/EBPβ that is currently in clinical evaluation in patients with advanced solid tumors.

Read more

Comprehensive Profiling of Poor-Risk Paired Primary and Recurrent Triple-Negative Breast Cancers Reveals Immune Phenotype Shifts

2020 – Katherine E. Hutchinson, Susan E. Yost, Ching-Wei Chang, Radia Marie Johnson, Adrian R. Carr, Paul R. McAdam, Daniel L. Halligan, Chun-Chieh Chang, Daniel Schmolze, Jackson Liang, and Yuan Yuan.

This study shows our collaboration with Genentech.

Read more

Development of a gene expression–based prognostic signature for IDH wild-type glioblastoma

2020 – Radia M. Johnson, Heidi S. Phillips, Carlos Bais, Cameron W. Brennan, Timothy F. Cloughesy, Anneleen Daemen, Ulrich Herrlinger, Robert B. Jenkins, Albert Lai, Christoph Mancao, Michael Weller, Wolfgang Wick, Richard Bourgon, and Josep Garcia.

This study shows our collaboration with Genentech.

Read more

Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma

2020 –Robin Kate Kelley, Tim Meyer, Lorenza Rimassa, Philippe Merle, Joong-Won Park, Thomas Yau, Stephen L. Chan, Jean-Frederic Blanc, Vincent C. Tam, Albert Tran, Vincenzo Dadduzio, David W. Markby, Rajesh Kaldate, Ann-Lii Cheng, Anthony B. El-Khoueiry, and Ghassan K. Abou-Alfa.

This study shows our collaboration with Exelixis.

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Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial

2019 – Antoinette R Tan, Gail S Wright, Anu R Thummala, et al.

This study shows our collaboration with G1 Therapeutics.

Trilaciclib is an intravenous cell-cycle inhibitor that transiently maintains immune cells and haemopoietic stem and progenitor cells in G1 arrest. By protecting the immune cells and bone marrow from chemotherapy-induced damage, trilaciclib has the potential to optimise antitumour activity while minimising myelotoxicity.

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Integration of genomic and transcriptomic data of inbred mouse models for polygenic obesity and leanness revealed “obese” and “lean” candidate alleles in polyadenylation signals

2024 – Martin Simon, Špela Mikec, Nicholas M. Morton, et al.

This study investigates the association between genetic variations in polyadenylation signals (PAS-SNPs) and obesity in inbred mouse models.

Read more

Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription

2023 – Melanie M. Frigault, Arushi Mithal, Harvey Wong, et al.

This study investigates the pharmacodynamic (PD) effect of CDK9 inhibition in preclinical models and in blood samples from patients (DH-DLBCL [n=10] and MYC+ NHL [n=5]) treated with 30 mg i.v. QW enitociclib.

Read more

Exploring the transcriptomic changes underlying recombinant vaccine efficacy against Teladorsagia circumcincta in 3-month-old lambs

2023 – Tara Pérez-Hernández, Julia N. Hernández, Stewart T.G. Burgess, et al.

Teladorsagia circumcincta is an abomasal parasitic nematode that can cause serious issues in small ruminant production, which are aggravated by drug resistance. Vaccines have been suggested as a feasible, long-lasting alternative for control since adaptation to the host’s immune mechanisms by helminths develops at a much slower pace than anthelmintic resistance. Recently, a T. circumcincta recombinant subunit vaccine yielded over a 60% reduction in egg excretion and worm burden and induced strong humoral and cellular anti-helminth responses in vaccinated 3-month-old Canaria Hair Breed (CHB) lambs, but Canaria Sheep (CS) of a similar age were not protected by the vaccine. Here, we compared the transcriptomic profiles in the abomasal lymph nodes of such 3-month-old CHB and CS vaccinates 40 days after infection with T. circumcincta to understand differences in responsiveness at the molecular level.

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Variability in the Response against Teladorsagia circumcincta in Lambs of Two Canarian Sheep Breeds

2022 –    Pérez-Hernández T.,  Hernández J., Machín C., McNeilly T. , Nisbet A. et al.

The increasing resistance to anthelmintics has necessitated the exploration of alternative control strategies of gastrointestinal nematode (GIN) infections. A sustainable option is genetic selection based on differences in susceptibility to GIN infection between and within breeds of sheep. Here, three-month-old Canaria Hair breed (GIN-resistant) and Canaria Sheep breed (GIN-susceptible) showed no significant between-breed differences after trickle infection with Teladorsagia circumcincta, whereas considerable individual variability was found in both breeds. Next, data from lambs of both breeds were used to explore the relationships between parasitological variables and T. circumcincta-specific IgA levels, local immune cell populations, and abomasal lymph node gene expression to understand the possible mechanisms underlying resistance. Mucosal IgA levels as well as numbers of globular leukocytes and MHC-II+ cells were associated with protection. Analysis of lymph node gene expression revealed the associations between lower parasite numbers and cumulative fecal egg counts and several immune pathways, such as leukocyte cell adhesion, activation and differentiation of T cells, in particular CD4+ and IL-4 production. The data obtained here may inform on the relationship between phenotypic resistance variability and protective responses at the humoral, cellular, and transcriptomic levels, thus contributing to identifying immune responses in young lambs that could be used as markers for selection.
(Just one of several genomics publications featuring bioinformatics research from Fios Genomics).

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Gene expression profiling of placentae from women with obesity and obstructive sleep apnoea

2022 – Emma C Johns, Daniel L Halligan, Triin Tammsalu, et al.

This study shows our collaboration with Queen’s Medical Research Institute.

Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised. 3′ mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9) were performed.

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Multiomics Provide Insights into the Key Molecules and Pathways Involved in the Physiological Adaptation of Atlantic Salmon ( Salmo salar) to Chemotherapeutic-Induced Oxidative Stress

2021 – Lazado C., Timmerhaus G., Breiland M., Pittman K., Hytterød S.

In this study, multiomics analysis helped understanding how a chemical oxidative stressor alters salmon physiology at both the systemic and mucosal levels. This knowledge will be pivotal in developing an evidence-driven approach to the use of oxidative therapeutics in fish, with some of the molecules and pathways identified as potential biomarkers and targets for assessing the physiological cost of these treatments.

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Consequences of continuous ozonation on the health and welfare of Atlantic salmon post-smolts in a brackish water recirculating aquaculture system

2021 – Lazado Carlo, Kevin T.Stiller, Britt-Kristin Megård Reiten, João Osório, Jelena Kolarevic, Lill-Heidi Johansen

This study investigated the biological consequences of 45-day continuous ozonation on Atlantic salmon (Salmo salar) post-smolts in a brackish water recirculating aquaculture system (RAS). Microarray analysis revealed that the gills and liver were more responsive to the oxidant than the skin, with the gills being the most sensitive. Moreover, the magnitude of the transcriptomic modifications depended on the exposure duration. A functional analysis showed that genes involved in immunity and ribosomal functions were significantly affected in the gills. In contrast, genes crucial for the oxidation-reduction process were mainly targeted in the liver.

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ctDNA guiding adjuvant immunotherapy in urothelial carcinoma

2021 – Thomas Powles, Zoe June Assaf, et al.

This study shows our collaboration with Genentech.

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse. This study evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer.

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Genome-wide analysis clarifies the population genetic structure of wild Gilthead Sea Bream (Sparus aurata)

2021 – Francesco Maroso, Konstantinos Gkagkavouzis, Sabina De Innocentiis, et al.

The study below shows our collaboration with the Aquatrace Consortium.

Gilthead sea bream is an important target for both recreational and commercial fishing in Europe, where it is also one of the most important cultured fish. These results are of fundamental importance for the development of proper management of this species in the wild and are a first step toward the study of the potential genetic impact of the sea bream aquaculture industry. (Just one of several genomics publications featuring bioinformatics research from Fios Genomics.)

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Serum Alpha-fetoprotein Levels and Clinical Outcomes in the Phase III CELESTIAL Study of Cabozantinib versus Placebo in Patients with Advanced Hepatocellular Carcinoma

2020 – Robin Kate Kelley, Tim Meyer, Lorenza Rimassa, et al.

This study shows our collaboration with Exelixis.

The phase III CELESTIAL study demonstrated improved overall survival (OS) and progression-free survival (PFS) with cabozantinib versus placebo in patients with previously treated, advanced hepatocellular carcinoma (HCC). We analyzed outcomes by baseline alpha-fetoprotein (AFP) and on-treatment AFP changes.

Read more

Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer

2020 – Marie-Claire Wagle, Joseph Castillo, Shrividhya Srinivasan, et al.

This study shows our collaboration with Genentech.

Prostate cancer is the second leading cause of cancer-related death in men. Our findings suggest that high tumor fusion burden may be a more appropriate biomarker than tumor mutational burden in prostate cancer, as it more closely associates with immunogenicity, and suggests that tumors with high fusion burden could be potential candidates for immunotherapeutic agents.

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Integration of genomic and transcriptomic data of inbred mouse models for polygenic obesity and leanness revealed “obese” and “lean” candidate alleles in polyadenylation signals

2024 – Martin Simon, Špela Mikec, Nicholas M. Morton, et al.

This study investigates the association between genetic variations in polyadenylation signals (PAS-SNPs) and obesity in inbred mouse models.

Read more

Microbe-host interplay in atopic dermatitis and psoriasis

2019 – Nanna Fyhrquist, Gareth Muirhead, Stefanie Prast-Nielsen, et al.

This study shows our collaboration with several organisations for the MAARS FP7 project

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis.

Read more

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