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Precision medicine risk prediction

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https://www.readbyqxmd.com/read/28926426/epigenetics-and-precision-oncology
#1
Rachael J Werner, Andrew D Kelly, Jean-Pierre J Issa
Epigenetic alterations such as DNA methylation defects and aberrant covalent histone modifications occur within all cancers and are selected for throughout the natural history of tumor formation, with changes being detectable in early onset, progression, and ultimately recurrence and metastasis. The ascertainment and use of these marks to identify at-risk patient populations, refine diagnostic criteria, and provide prognostic and predictive factors to guide treatment decisions are of growing clinical relevance...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28916927/genetic-test-risk-prediction-and-counseling
#2
Maggie Haitian Wang, Haoyi Weng
Advancement in technology has nurtured the new era of genetic tests for personalized medicine. In this chapter, we will introduce the current development, challenges, and the outlook of genetic test, disease risk prediction, and genetic counseling. In the first section, we will present the success cases in the areas of molecular classification of tumors, pharmacogenomics, and Mendelian disorders, and the challenges of genetic tests implementations. In the second section, common methods for genetic risk prediction models and evaluation measures will be introduced, as well as challenges in feature reliability, risk model stability, and clinical utility...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28877177/an-in-vitro-diagnostic-certified-point-of-care-single-nucleotide-test-for-il28b-polymorphisms
#3
Darragh Duffy, Estelle Mottez, Shaun Ainsworth, Tan-Phuc Buivan, Aurelie Baudin, Muriel Vray, Ben Reed, Arnaud Fontanet, Alexandra Rohel, Ventzislava Petrov-Sanchez, Laurent Abel, Ioannis Theodorou, Gino Miele, Stanislas Pol, Matthew L Albert
Numerous genetic polymorphisms have been identified as associated with disease or treatment outcome, but the routine implementation of genotyping into actionable medical care remains limited. Point-of-care (PoC) technologies enable rapid and real-time treatment decisions, with great potential for extending molecular diagnostic approaches to settings with limited medical infrastructure (e.g., CLIA certified diagnostic laboratories). With respect to resource-limited settings, there is a need for simple devices to implement biomarker guided treatment strategies...
2017: PloS One
https://www.readbyqxmd.com/read/28874244/the-interplay-between-fasting-glucose-echocardiography-and-biomarkers-pathophysiological-considerations-and-prognostic-implications
#4
Manan Pareek
BACKGROUND: Traditional cardiovascular risk stratification tools that employ clinical risk factors are limited by their modest discriminative abilities. As such, robust cardiovascular risk assessment, including our understanding of the complex interplay between risk factors, in the primary preventive setting, remains incomplete. Phenotypical heterogeneity may be even greater among subjects with hyperglycemic conditions, i.e., prediabetes and diabetes, which is worrisome, given the dramatic global rise in mean fasting glucose levels, and the strong association with adverse cardiovascular outcomes...
September 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/28863391/a-precision-medicine-approach-for-psychiatric-disease-based-on-repeated-symptom-scores
#5
Anthony T Fojo, Katherine L Musliner, Peter P Zandi, Scott L Zeger
For psychiatric diseases, rich information exists in the serial measurement of mental health symptom scores. We present a precision medicine framework for using the trajectories of multiple symptoms to make personalized predictions about future symptoms and related psychiatric events. Our approach fits a Bayesian hierarchical model that estimates a population-average trajectory for all symptoms and individual deviations from the average trajectory, then fits a second model that uses individual symptom trajectories to estimate the risk of experiencing an event...
August 11, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28860053/blood-brain-barrier-adapted-precision-medicine-therapy-for-pediatric-brain-tumors
#6
Bernard L Marini, Lydia L Benitez, Andrew H Zureick, Ralph Salloum, Angela C Gauthier, Julia Brown, Yi-Mi Wu, Dan R Robinson, Chandan Kumar, Robert Lonigro, Pankaj Vats, Xuhong Cao, Katayoon Kasaian, Bailey Anderson, Brendan Mullan, Benjamin Chandler, Joseph R Linzey, Sandra I Camelo-Piragua, Sriram Venneti, Paul E McKeever, Kathryn A McFadden, Andrew P Lieberman, Noah Brown, Lina Shao, Marcia A S Leonard, Larry Junck, Erin McKean, Cormac O Maher, Hugh J L Garton, Karin M Muraszko, Shawn Hervey-Jumper, Jean M Mulcahy-Levy, Adam Green, Lindsey M Hoffman, Katie Dorris, Nicholas A Vitanza, Joanne Wang, Jonathan Schwartz, Rishi Lulla, Natasha Pillay Smiley, Miriam Bornhorst, Daphne A Haas-Kogan, Patricia L Robertson, Arul M Chinnaiyan, Rajen Mody, Carl Koschmann
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28838408/crohn-s-disease-genetics-update
#7
REVIEW
Ming-Hsi Wang, Michael F Picco
Since the discovery of the first Crohn's disease (CD) gene NOD2 in 2001, 140 genetic loci have been found in whites using high-throughput genome-wide association studies. Several genes influence the CD subphenotypes and treatment response. With the observations of increasing prevalence in Asia and developing countries and the incomplete explanation of CD variance, other underexplored areas need to be integrated through novel methodologies. Algorithms that incorporate specific genetic risk alleles with other biomarkers will be developed and used to predict CD disease course, complications, and response to specific therapies, allowing precision medicine to become real in CD...
September 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28815129/sdt-a-tree-method-for-detecting-patient-subgroups-with-personalized-risk-factors
#8
Xiangrui Li, Dongxiao Zhu, Ming Dong, Milad Zafar Nezhad, Alexander Janke, Phillip D Levy
Eradicating health disparity is a new focus for precision medicine research. Identifying patient subgroups is an effective approach to customized treatments for maximizing efficiency in precision medicine. Some features may be important risk factors for specific patient subgroups but not necessarily for others, resulting in a potential divergence in treatments designed for a given population. In this paper, we propose a tree-based method, called Subgroup Detection Tree (SDT), to detect patient subgroups with personalized risk factors...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#9
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
September 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28757202/leveraging-multi-ethnic-evidence-for-risk-assessment-of-quantitative-traits-in-minority-populations
#10
Marc A Coram, Huaying Fang, Sophie I Candille, Themistocles L Assimes, Hua Tang
An essential component of precision medicine is the ability to predict an individual's risk of disease based on genetic and non-genetic factors. For complex traits and diseases, assessing the risk due to genetic factors is challenging because it requires knowledge of both the identity of variants that influence the trait and their corresponding allelic effects. Although the set of risk variants and their allelic effects may vary between populations, a large proportion of these variants were identified based on studies in populations of European descent...
August 3, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28744848/systems-and-precision-medicine-approaches-to-diabetes-heterogeneity-a-big-data-perspective
#11
Enrico Capobianco
Big Data, and in particular Electronic Health Records, provide the medical community with a great opportunity to analyze multiple pathological conditions at an unprecedented depth for many complex diseases, including diabetes. How can we infer on diabetes from large heterogeneous datasets? A possible solution is provided by invoking next-generation computational methods and data analytics tools within systems medicine approaches. By deciphering the multi-faceted complexity of biological systems, the potential of emerging diagnostic tools and therapeutic functions can be ultimately revealed...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28740468/evolution-of-precision-medicine-and-surgical-strategies-for-bicuspid-aortic-valve-associated-aortopathy
#12
Ali Fatehi Hassanabad, Alex J Barker, David Guzzardi, Michael Markl, Chris Malaisrie, Patrick M McCarthy, Paul W M Fedak
Bicuspid aortic valve (BAV) is a common congenital cardiac malformation affecting 1-2% of people. BAV results from fusion of two adjacent aortic valve cusps, and is associated with dilatation of the aorta, known as bicuspid valve associated aortopathy. Bicuspid valve aortopathy is progressive and associated with catastrophic clinical events, such as aortic dissection and rupture. Therefore, frequent monitoring and early intervention with prophylactic surgical resection of the proximal aorta is often recommended...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28686075/pharmacogenetics-and-the-treatment-of-functional-gastrointestinal-disorders
#13
Houssam Halawi, Michael Camilleri
The diagnosis and management of functional gastrointestinal disorders (FGIDs) remain very challenging. In the era of precision medicine, it is important to individualize the treatment of these conditions by providing targeted and effective therapies while minimizing the risk of medication side effects. By using genetic information that predicts and affects the responses to specific medications, it is anticipated that the science of pharmacogenetics in FGIDs will advance the practice of precision medicine. The pathophysiology of FGIDs is complex, involving the interaction between predisposing genetic and environmental factors...
July 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28665803/methylation-differences-reveal-heterogeneity-in-preterm-pathophysiology-results-from-bipartite-network-analyses
#14
Suresh K Bhavnani, Bryant Dang, Varun Kilaru, Maria Caro, Shyam Visweswaran, George Saade, Alicia K Smith, Ramkumar Menon
BACKGROUND: Recent studies have shown that epigenetic differences can increase the risk of spontaneous preterm birth (PTB). However, little is known about heterogeneity underlying such epigenetic differences, which could lead to hypotheses for biological pathways in specific patient subgroups, and corresponding targeted interventions critical for precision medicine. Using bipartite network analysis of fetal DNA methylation data we demonstrate a novel method for classification of PTB. METHODS: The data consisted of DNA methylation across the genome (HumanMethylation450 BeadChip) in cord blood from 50 African-American subjects consisting of 22 cases of early spontaneous PTB (24-34 weeks of gestation) and 28 controls (>39 weeks of gestation)...
June 30, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28654205/driving-toward-precision-medicine-for-acute-leukemias-are-we-there-yet
#15
REVIEW
Clement Chung, Hilary Ma
Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias...
September 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28636403/applying-precision-medicine-to-trial-design-using-physiology-extracorporeal-co2-removal-for-acute-respiratory-distress-syndrome
#16
REVIEW
Ewan C Goligher, Marcelo B P Amato, Arthur S Slutsky
In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO2 removal (ECCO2R) for ultraprotective ventilation in ARDS...
September 1, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28634997/working-toward-precision-medicine-predicting-phenotypes-from-exomes-in-the-critical-assessment-of-genome-interpretation-cagi-challenges
#17
Roxana Daneshjou, Yanran Wang, Yana Bromberg, Samuele Bovo, Pier L Martelli, Giulia Babbi, Pietro Di Lena, Rita Casadio, Matthew Edwards, David Gifford, David T Jones, Laksshman Sundaram, Rajendra Rana Bhat, Xiaolin Li, Lipika R Pal, Kunal Kundu, Yizhou Yin, John Moult, Yuxiang Jiang, Vikas Pejaver, Kymberleigh A Pagel, Biao Li, Sean D Mooney, Predrag Radivojac, Sohela Shah, Marco Carraro, Alessandra Gasparini, Emanuela Leonardi, Manuel Giollo, Carlo Ferrari, Silvio C E Tosatto, Eran Bachar, Johnathan R Azaria, Yanay Ofran, Ron Unger, Abhishek Niroula, Mauno Vihinen, Billy Chang, Maggie H Wang, Andre Franke, Britt-Sabina Petersen, Mehdi Pirooznia, Peter Zandi, Richard McCombie, James B Potash, Russ B Altman, Teri E Klein, Roger A Hoskins, Susanna Repo, Steven E Brenner, Alexander A Morgan
Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge...
September 2017: Human Mutation
https://www.readbyqxmd.com/read/28624849/the-accuracy-of-68-ga-psma-pet-ct-in-primary-lymph-node-staging-in-high-risk-prostate-cancer
#18
Can Öbek, Tünkut Doğanca, Emre Demirci, Meltem Ocak, Ali Rıza Kural, Asıf Yıldırım, Uğur Yücetaş, Çetin Demirdağ, Sarper M Erdoğan, Levent Kabasakal
PURPOSE: To assess the diagnostic accuracy of (68)Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging. METHODS: This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included...
June 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28598966/joint-modeling-of-genetically-correlated-diseases-and-functional-annotations-increases-accuracy-of-polygenic-risk-prediction
#19
Yiming Hu, Qiongshi Lu, Wei Liu, Yuhua Zhang, Mo Li, Hongyu Zhao
Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS) in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28594818/leveraging-functional-annotations-in-genetic-risk-prediction-for-human-complex-diseases
#20
Yiming Hu, Qiongshi Lu, Ryan Powles, Xinwei Yao, Can Yang, Fang Fang, Xinran Xu, Hongyu Zhao
Genetic risk prediction is an important goal in human genetics research and precision medicine. Accurate prediction models will have great impacts on both disease prevention and early treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome wide association studies (GWAS), genetic risk prediction accuracy remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes in the presence of linkage disequilibrium...
June 2017: PLoS Computational Biology
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