Haplotyping germline and cancer genomes with high-throughput linked-read sequencing.

Haplotyping of human chromosomes is a prerequisite for cataloguing the full repertoire of genetic variation. We present a microfluidics-based, linked-read sequencing technology that can phase and haplotype germline and cancer genomes using nanograms of input DNA. This high-throughput platform prepares barcoded libraries for short-read sequencing and computationally reconstructs long-range haplotype and structural variant information. We generate haplotype blocks in a nuclear trio that are concordant with expected inheritance patterns and phase a set of structural variants. We also resolve the structure of the EML4-ALK gene fusion in the NCI-H2228 cancer cell line using phased exome sequencing. Finally, we assign genetic aberrations to specific megabase-scale haplotypes generated from whole-genome sequencing of a primary colorectal adenocarcinoma. This approach resolves haplotype information using up to 100 times less genomic DNA than some methods and enables the accurate detection of structural variants.

Mental health indicator interaction in predicting substance abuse treatment outcomes in nevada.

BACKGROUND: Indicators of co-occurring mental health and substance abuse problems routinely collected at treatment admission in 19 State substance abuse treatment systems include a dual diagnosis and a State mental health (cognitive impairment) agency referral. These indicators have yet to be compared as predictors of treatment outcomes. OBJECTIVES: 1. Compare both indices as outcomes predictors individually and interactively. 2. Assess relationship of both indices to other client risk factors, e.g., physical/sexual abuse. METHODS: Client admission and discharge records from the Nevada substance abuse treatment program, spanning 1995-2001 were reviewed (n = 17,591). Logistic regression analyses predicted treatment completion with significant improvement (33%) and treatment readmission following discharge (21%). Using Cox regression, the number of days from discharge to treatment readmission was predicted. Examined as predictors were two mental health indicators and their interaction with other admission and treatment variables controlled. RESULTS: Neither mental health indicator alone significantly predicted any of the three outcomes; however, the interaction between the two indicators significantly predicted each outcome (p < .05). Having both indices was highly associated with physical/sexual abuse, domestic violence, homelessness, out of labor force and prior treatment. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Indicator interactions may help improve substance abuse treatment outcomes prediction.

Effectiveness of long-term residential substance abuse treatment for women: findings from three national studies.

The effectiveness of residential substance abuse treatment for women was examined using data from the Center for Substance Abuse Treatment's Residential Women and Children/Pregnant and Postpartum Women (RWC/PPW) Cross-Site Study and two other recent national studies. Treatment success was defined as posttreatment abstinence from further drug or alcohol use, measured through in-person follow-up interviews conducted 6-12 months after each client's discharge. Despite differences in treatment programs, client profiles, follow-up intervals, data collection methods, and other factors, all three studies found high treatment success rates--ranging narrowly from 68% to 71% abstinent--among women who spent six months or more in treatment. Success rates were lower, and between-study differences were larger, for clients with shorter stays in treatment. Controlling for salient client and treatment project characteristics, strong associations between length of stay in treatment and posttreatment abstinence rate were found in all three studies, suggesting that women's length of stay in residential treatment is a major determinant of treatment effectiveness. In further analysis of RWC/PPW data, treatment completion was also found to be an important outcome factor. Among clients who remained in treatment for at least three months, those who achieved their treatment goals in three to five months abstinence outcomes were as good as those for clients who took more than six months to complete their treatment (76%-78% abstinent) and substantially better than those for clients who did not complete treatment (51%-52% abstinent). Notably, however, most of the RWC/PPW clients who successfully completed treatment (71%) required six months or more to do so.