Quality assessment and refinement of chromatin accessibility data using a sequence-based predictive model

Chromatin accessibility assays are central to the genome-wide identification of gene regulatory elements associated with transcriptional regulation. However, the data have highly variable quality arising from several biological and technical factors. To surmount this problem, we developed a sequence-based machine learning method to evaluate and refine chromatin accessibility data. Our framework, gapped k-mer SVM quality check (gkmQC), provides the quality metrics for a sample based on the prediction accuracy of the trained models. We tested 886 DNase-seq samples from the ENCODE/Roadmap projects to demonstrate that gkmQC can effectively identify high-quality (HQ) samples with low conventional quality scores owing to marginal read depths. Peaks identified in HQ samples are more accurately aligned at functional regulatory elements, show greater enrichment of regulatory elements harboring functional variants, and explain greater heritability of phenotypes from their relevant tissues. Moreover, gkmQC can optimize the peak-calling threshold to identify additional peaks, especially for rare cell types in single-cell chromatin accessibility data

Predictive validity and correlates of selfâ assessed resilience among U.S. Army soldiers

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142339/1/da22694.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142339/2/da22694_am.pd

Alcohol Misuse and Coâ Occurring Mental Disorders Among New Soldiers in the U.S. Army

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135492/1/acer13269_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135492/2/acer13269.pd

Design of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multi‐component epidemiological and neurobiological study designed to generate actionable evidence‐based recommendations to reduce US Army suicides and increase basic knowledge about the determinants of suicidality. This report presents an overview of the designs of the six components of the Army STARRS. These include: an integrated analysis of the Historical Administrative Data Study (HADS) designed to provide data on significant administrative predictors of suicides among the more than 1.6 million soldiers on active duty in 2004–2009; retrospective case‐control studies of suicide attempts and fatalities; separate large‐scale cross‐sectional studies of new soldiers (i.e. those just beginning Basic Combat Training [BCT], who completed self‐administered questionnaires [SAQs] and neurocognitive tests and provided blood samples) and soldiers exclusive of those in BCT (who completed SAQs); a pre‐post deployment study of soldiers in three Brigade Combat Teams about to deploy to Afghanistan (who completed SAQs and provided blood samples) followed multiple times after returning from deployment; and a platform for following up Army STARRS participants who have returned to civilian life. Department of Defense/Army administrative data records are linked with SAQ data to examine prospective associations between self‐reports and subsequent suicidality. The presentation closes with a discussion of the methodological advantages of cross‐component coordination. Copyright © 2013 John Wiley & Sons, Ltd .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102177/1/mpr1401.pd

Prognostic Indicators of Persistent Post-Concussive Symptoms after Deployment-Related Mild Traumatic Brain Injury: A Prospective Longitudinal Study in U.S. Army Soldiers

Mild traumatic brain injury (mTBI), or concussion, is prevalent in the military. The course of recovery can be highly variable. This study investigates whether deployment-acquired mTBI is associated with subsequent presence and severity of post-concussive symptoms (PCS) and identifies predictors of persistent PCS among US Army personnel who sustained mTBI while deployed to Afghanistan. We used data from a prospective longitudinal survey of soldiers assessed 1?2 months before a 10-month deployment to Afghanistan (T0), on redeployment to the United States (T1), approximately 3 months later (T2), and approximately 9 months later (T3). Outcomes of interest were PCS at T2 and T3. Predictors considered were: sociodemographic factors, number of previous deployments, pre-deployment mental health and TBI history, and mTBI and other military-related stress during the index deployment. The study sample comprised 4518 soldiers, 822 (18.2%) of whom experienced mTBI during the index deployment. After adjusting for demographic, clinical, and deployment-related factors, deployment-acquired mTBI was associated with nearly triple the risk of reporting any PCS and with increased severity of PCS when symptoms were present. Among those who sustained mTBI, severity of PCS at follow-up was associated with history of pre-deployment TBI(s), pre-deployment psychological distress, more severe deployment stress, and loss of consciousness or lapse of memory (versus being ?dazed? only) as a result of deployment-acquired mTBI. In summary, we found that sustaining mTBI increases risk for persistent PCS. Previous TBI(s), pre-deployment psychological distress, severe deployment stress, and loss of consciousness or lapse of memory resulting from mTBI(s) are prognostic indicators of persistent PCS after an index mTBI. These observations may have actionable implications for prevention of chronic sequelae of mTBI in the military and other settings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140173/1/neu.2015.4320.pd

Renal and Cardiovascular Morbidities Associated with APOL1 Status among African-American and Non-African-American Children with Focal Segmental Glomerulosclerosis

Background and objectives: African American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression and cardiovascular morbidity in children. Design, setting, participants, & measurements: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease.Results: A total of 140 AA children in the CKiD study were genotyped. HR APOL1 genotypes were present in 24% of AA children (33/140) and were associated with FSGS, p 3 mg/L (33% vs. 15%, p=0.12) and obesity (48% vs. 19%, p=0.01). There were no differences in glomerular filtration rate, hemoglobin, iPTH, or calcium-phosphate product. Conclusions: AA children with HR APOL1 genotype and FSGS have increase prevalence of obesity and LVH despite a later age of FSGS onset, while adjusting for socioeconomic status. Treatment of obesity may be an important component of CKD and LVH management in this population

Field procedures in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multi‐component epidemiological and neurobiological study of unprecedented size and complexity designed to generate actionable evidence‐based recommendations to reduce US Army suicides and increase basic knowledge about determinants of suicidality by carrying out coordinated component studies. A number of major logistical challenges were faced in implementing these studies. The current report presents an overview of the approaches taken to meet these challenges, with a special focus on the field procedures used to implement the component studies. As detailed in the paper, these challenges were addressed at the onset of the initiative by establishing an Executive Committee, a Data Coordination Center (the Survey Research Center [SRC] at the University of Michigan), and study‐specific design and analysis teams that worked with staff on instrumentation and field procedures. SRC staff, in turn, worked with the Office of the Deputy Under Secretary of the Army (ODUSA) and local Army Points of Contact (POCs) to address logistical issues and facilitate data collection. These structures, coupled with careful fieldworker training, supervision, and piloting, contributed to the major Army STARRS data collection efforts having higher response rates than previous large‐scale studies of comparable military samples. Copyright © 2013 John Wiley & Sons, Ltd .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102238/1/mpr1400.pd

Screening archaeological bone for palaeogenetic and palaeoproteomic studies.

The recovery and analysis of ancient DNA and protein from archaeological bone is time-consuming and expensive to carry out, while it involves the partial or complete destruction of valuable or rare specimens. The fields of palaeogenetic and palaeoproteomic research would benefit greatly from techniques that can assess the molecular quality prior to sampling. To be relevant, such screening methods should be effective, minimally-destructive, and rapid. This study reports results based on spectroscopic (Fourier-transform infrared spectroscopy in attenuated total reflectance [FTIR-ATR]; n = 266), palaeoproteomic (collagen content; n = 226), and palaeogenetic (endogenous DNA content; n = 88) techniques. We establish thresholds for three different FTIR indices, a) the infrared splitting factor [IRSF] that assesses relative changes in bioapatite crystals' size and homogeneity; b) the carbonate-to-phosphate [C/P] ratio as a relative measure of carbonate content in bioapatite crystals; and c) the amide-to-phosphate ratio [Am/P] for assessing the relative organic content preserved in bone. These thresholds are both extremely reliable and easy to apply for the successful and rapid distinction between well- and poorly-preserved specimens. This is a milestone for choosing appropriate samples prior to genomic and collagen analyses, with important implications for biomolecular archaeology and palaeontology

Response bias, weighting adjustments, and design effects in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multi‐component epidemiological and neurobiological study designed to generate actionable recommendations to reduce US Army suicides and increase knowledge about determinants of suicidality. Three Army STARRS component studies are large‐scale surveys: one of new soldiers prior to beginning Basic Combat Training (BCT; n  = 50,765 completed self‐administered questionnaires); another of other soldiers exclusive of those in BCT ( n  = 35,372); and a third of three Brigade Combat Teams about to deploy to Afghanistan who are being followed multiple times after returning from deployment ( n  = 9421). Although the response rates in these surveys are quite good (72.0–90.8%), questions can be raised about sample biases in estimating prevalence of mental disorders and suicidality, the main outcomes of the surveys based on evidence that people in the general population with mental disorders are under‐represented in community surveys. This paper presents the results of analyses designed to determine whether such bias exists in the Army STARRS surveys and, if so, to develop weights to correct for these biases. Data are also presented on sample inefficiencies introduced by weighting and sample clustering and on analyses of the trade‐off between bias and efficiency in weight trimming. Copyright © 2013 John Wiley & Sons, Ltd .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102203/1/mpr1399.pd