Integrated genomic analyses in PDX model reveal a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for nasopharyngeal carcinoma.

Related Articles Integrated genomic analyses in PDX model reveal a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for nasopharyngeal carcinoma. J Exp Clin…

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Circulating Long Noncoding RNAs as Biomarkers for Predicting Head and Neck Squamous Cell Carcinoma.

Related Articles Circulating Long Noncoding RNAs as Biomarkers for Predicting Head and Neck Squamous Cell Carcinoma. Cell Physiol Biochem. 2018;50(4):1429-1440 Authors: Yao Y, Chen X,…

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A High-Resolution Genetic Map for the Laboratory Rat.

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A High-Resolution Genetic Map for the Laboratory Rat.

G3 (Bethesda). 2018 07 02;8(7):2241-2248

Authors: Littrell J, Tsaih SW, Baud A, Rastas P, Solberg-Woods L, Flister MJ

Abstract
An accurate and high-resolution genetic map is critical for mapping complex traits, yet the resolution of the current rat genetic map is far lower than human and mouse, and has not been updated since the original Jensen-Seaman map in 2004. For the first time, we have refined the rat genetic map to sub-centimorgan (cM) resolution (<0.02 cM) by using 95,769 genetic markers and 870 informative meioses from a cohort of 528 heterogeneous stock (HS) rats. Global recombination rates in the revised sex-averaged map (0.66 cM/Mb) did not differ compared to the historical map (0.65 cM/Mb); however, substantial refinement was made to the localization of highly recombinant regions within the revised map. Also for the first time, sex-specific rat genetic maps were generated, which revealed both genomewide and fine-scale variation in recombination rates between male and female rats. Reanalysis of multiple quantitative trait loci (QTL) using the historical and refined rat genetic maps demonstrated marked changes to QTL localization, shape, and effect size. As a resource to the rat research community, we have provided revised centimorgan positions for all physical positions within the rat genome and commonly used genetic markers for trait mapping, including 44,828 SSLP markers and the RATDIV genotyping array. Collectively, this study provides a substantial improvement to the rat genetic map and an unprecedented resource for analysis of complex traits and recombination in the rat.

PMID: 29760201 [PubMed – indexed for MEDLINE]

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Understanding and Predicting Antidepressant Response: Using Animal Models to Move Toward Precision Psychiatry.

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Understanding and Predicting Antidepressant Response: Using Animal Models to Move Toward Precision Psychiatry.

Front Psychiatry. 2018;9:512

Authors: Herzog DP, Beckmann H, Lieb K, Ryu S, Müller MB

Abstract
There are two important gaps of knowledge in depression treatment, namely the lack of biomarkers predicting response to antidepressants and the limited knowledge of the molecular mechanisms underlying clinical improvement. However, individually tailored treatment strategies and individualized prescription are greatly needed given the huge socio-economic burden of depression, the latency until clinical improvement can be observed and the response variability to a particular compound. Still, individual patient-level antidepressant treatment outcomes are highly unpredictable. In contrast to other therapeutic areas and despite tremendous efforts during the past years, the genomics era so far has failed to provide biological or genetic predictors of clinical utility for routine use in depression treatment. Specifically, we suggest to (1) shift the focus from the group patterns to individual outcomes, (2) use dimensional classifications such as Research Domain Criteria, and (3) envision better planning and improved connections between pre-clinical and clinical studies within translational research units. In contrast to studies in patients, animal models enable both searches for peripheral biosignatures predicting treatment response and in depth-analyses of the neurobiological pathways shaping individual antidepressant response in the brain. While there is a considerable number of animal models available aiming at mimicking disease-like conditions such as those seen in depressive disorder, only a limited number of preclinical or truly translational investigations is dedicated to the issue of heterogeneity seen in response to antidepressant treatment. In this mini-review, we provide an overview on the current state of knowledge and propose a framework for successful translational studies into antidepressant treatment response.

PMID: 30405454 [PubMed]

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