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Hong H.,National Center for Toxicological Research (NCTR) | Goodsaid F.,Genomics Group | Shi L.,National Center for Toxicological Research (NCTR) | Tong W.,National Center for Toxicological Research (NCTR)
Biomarkers in Medicine | Year: 2010

Molecular biomarkers are used for various purposes, including disease diagnosis and prognosis, prediction and assessment of treatment response, and safety assessment. There has been a significant increase in the number of US FDA-approved drug labels containing information on molecular biomarkers over the last decade. Almost every pharmaceutical company has been developing molecular biomarker programs, either alone, through partnerships or other ventures. More molecular biomarkers are expected to be identified and validated in drug development, and used to support approval of drug products. This article summarizes the current status of molecular biomarkers used for FDA-approved drug products, and discusses the challenges and future perspectives for the identification and qualification of molecular biomarkers. Specific FDA programs and research projects related to molecular biomarkers are also discussed for supporting regulatory review in the future. © 2010 Future Medicine Ltd.


Tesch G.,Monash Medical Center | Amur S.,Genomics Group | Schousboe J.T.,Minneapolis | Schousboe J.T.,University of Minnesota | And 3 more authors.
AAPS Journal | Year: 2010

Biomarkers are important tools for identifying and stratifying diseases, predicting their progression and determining the effectiveness, safety, and doses of therapeutic interventions. This is important for common chronic diseases such as diabetic nephropathy, osteoporosis, and rheumatoid arthritis which affect large numbers of patients worldwide. This article summarizes the current knowledge of established and novel biomarkers for each of these diseases as presented at the 2008 AAPS/ACCP joint symposium "Success Achieved and Challenges Ahead in Translating Biomarkers into Clinical Applications," in Atlanta, Georgia. The advantages and disadvantages of various proteomic, metabolomic, genomic, and imaging biomarkers are discussed in relation to disease diagnosis and stratification, prognosis, drug development, and potential clinical applications. The use of biomarkers as a means to determine therapeutic interventions is also considered. In addition, we show that biomarkers may be useful for adapting therapies for individual needs by allowing the selection of patients who are most likely to respond or react adversely to a particular treatment. They may also be used to determine whether the development of a novel therapy is worth pursuing by informing crucial go/no go decisions around safety and efficacy. Indeed, regulatory bodies now suggest that effective integration of biomarkers into clinical drug development programs is likely to promote the development of novel therapeutics and more personalized medicine. © 2010 American Association of Pharmaceutical Scientists.


News Article | April 28, 2016
Site: www.biosciencetechnology.com

An important model in studying human disease, the non-coding RNA of the canine genome is an essential starting point for evolutionary and biomedical studies -- according to a new study led by The Genome Analysis Centre (TGAC). New research published today in PLOS ONE reveals an improved annotation of microRNAs in the dog genome to further understand its biological role. Providing a platform for future studies into biomedicine, evolution and the domestication of important animals including dogs, cows, horses and pigs. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in regulating gene expression in animals and plants. Using the latest dog genome assembly and small RNA sequences of nine different dog tissues including skin, blood, ovaries and testes, scientists from TGAC have identified 91 novel miRNAs. This discovery provides a significant opportunity not only to enhance our understanding of how miRNAs regulate a variety of biological processes in an important model species for studying human diseases, but can lead to further, similar research into the role that miRNAs play in animal domestication. Lead researcher, Dr. Luca Penso Dolfin from TGAC's Vertebrate & Health Genomics Group, said: "As miRNAs are so important in orchestrating a variety of cellular processes, the discovery of these 91 novel miRNAs provides a vital starting point to explore their potentially major effects on gene regulation." Overall, 811 miRNAs were analyzed by Dr. Penso-Dolfin: 91 novel microRNA sequences and 720 conserved (that is, common to other organisms). Among these conserved loci, 207 had not previously been identified as canine microRNAs. Dr. Penso-Dolfin, added: "Our results represent a clear improvement in our knowledge of the dog genome, paving the way for further research on the evolution of gene regulation, and the contribution of microRNAs to pathological conditions. We are now looking at additional data for dog and a variety of farm animals, combining microRNA discovery to the investigation of their possible role in domestication." The domestic dog, Canis familiaris, is the result of wolf (Canis lupus) domestication, which started around 10,000 years ago. Since then, hundreds of dog breeds have been artificially selected, leading to very high levels of morphological and behavioural variation. Having shared the environment with humans ever since its appearance, the dog has been exposed to similar pathogens, and therefore represents an important model system for the study of human diseases. The publication of the latest Canine genome build and annotation, CanFam3.1 provides an opportunity to enhance our understanding of gene regulation across tissues in the dog model system.


Zhang L.,Genomics Group | Yin S.,Genomics Group | Miclaus K.,SAS Institute | Chierici M.,Fondazione Bruno Kessler | And 6 more authors.
Pharmacogenomics Journal | Year: 2010

The robustness of genome-wide association study (GWAS) results depends on the genotyping algorithms used to establish the association. This paper initiated the assessment of the impact of the Corrected Robust Linear Model with Maximum Likelihood Classification (CRLMM) genotyping quality on identifying real significant genes in a GWAS with large sample sizes. With microarray image data from the Wellcome Trust Case-Control Consortium (WTCCC), 1991 individuals with coronary artery disease (CAD) and 1500 controls, genetic associations were evaluated under various batch sizes and compositions. Experimental designs included different batch sizes of 250, 350, 500, 2000 samples with different distributions of cases and controls in each batch with either randomized or simply combined (4:3 case-control ratios) or separate case-control samples as well as whole 3491 samples. The separate composition could create 2-3% discordance in the single nucleotide polymorphism (SNP) results for quality control/statistical analysis and might contribute to the lack of reproducibility between GWAS. CRLMM shows high genotyping accuracy and stability to batch effects. According to the genotypic and allelic tests (P5.0 × 10 -7), nine significant signals on chromosome 9 were found consistently in all batch sizes with combined design. Our findings are critical to optimize the reproducibility of GWAS and confirm the genetic role in the pathophysiology of CAD. © 2010 Macmillan Publishers Limited. All rights reserved.


Zineh I.,Genomics Group | Mummaneni P.,Genomics Group | Lyndly J.,Center for Drug Evaluation and Research | Amur S.,Genomics Group | And 4 more authors.
Pharmacogenomics | Year: 2011

Use of pharmacogenetics to inform treatment decisions remains a priority for clinicians, patients and public health agencies. We previously developed a framework for systematically assessing whether pharmacogenetic test information would likely bring value to clinical decision-making and enjoy practical uptake. We applied this tool to allopurinol to determine potential usefulness of HLA genetic information in assessing risk for allopurinol-induced severe cutaneous adverse reactions. We quantified allopurinol use data and the magnitude of adverse event signals using US FDA databases, reviewed reported cases of allopurinol-associated severe cutaneous adverse reactions to assess whether clinical subtypes of patients could be identified, performed pooled analyses of associations between HLA variation and allopurinol-induced severe cutaneous adverse reactions and described considerations in clinical implementation of allopurinol pharmacogenetics. © 2011 Future Medicine Ltd.

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