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Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.

Hybridization presents a unique challenge for conservation biologists and managers. While hybridization is an important evolutionary process, hybridization is also a threat formany native species. The endangered species recovery effort for the red wolf Canis rufus is a classic system for understanding and addressing the challenges of hybridization. From 1987?1993, 63 red wolves were released from captivity in eastern North Carolina, USA, to establish a free-ranging, non-essential experimental population. By 1999, managers recognized hybridization with invasive coyotes Canis latrans was the single greatest threat to successful recovery, and an adaptive management plan was adopted with innovative approaches for managing the threat of hybridization. Here we review the application and results of the adaptive management efforts from 1993 to 2013 by comparing: (1) the numbers of wolves, coyotes, and hybrids captured, (2) the numbers of territorial social groups with presumed breeding capabilities, (3) the number of red wolf and hybrid litters documented each year and (4) the degree of coyote introgression into the wild red wolf gene pool. We documented substantial increases in the number of known red wolves and red wolf social groups from 1987–2004 followed by a plateau and slight decline by 2013.The number of red wolf litters exceeded hybrid litters each year and the proportion of hybrid litters per year averaged 21%. The genetic composition of the wild red wolf population is estimated to include < 4% coyote ancestry from recent introgression since reintroduction. We conclude that the adaptive management plan was effective at reducing the introgression of coyote genes into the red wolf population, but population recovery of red wolves will require continuation of the current management plan, or alternative approaches, for the foreseeable future. More broadly, we discuss the lessons learned from red wolf adaptive management that could assist other endangered species recovery efforts facing the challenge of minimizing hybridization.

Background A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults. Methods Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose. Results V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination. Conclusions V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection. Clinical Trial Registration . NCT01986010.

The United States Fish and Wildlife Service (USFWS) developed guidelines for the composition and role of endangered species recovery implementation teams, but few teams have been established and their success has not been evaluated. Using the recovery program of the red wolf (Canis rufus) as a model, we describe the genesis, function, and success of the Red Wolf Recovery Implementation Team (RWRIT) in helping guide the establishment of a viable red wolf population in eastern North Carolina. In operation since 1999, the RWRIT meets bi‐annually to review USFWS progress and provide recommendations aimed at maximizing success of species recovery. The team is comprised of 8 research scientists from disciplines including population genetics, canid ecology, population ecology, veterinary medicine, and captive management. Representation from each of these disciplines is deemed necessary for proper evaluation of recovery progress and assessment of future needs. Meeting attendance by the USFWS field management team ensures both proper reporting of past progress and future implementation of management recommendations. Over time, RWRIT members have assumed specific assignments for data analyses, further contributing to the recovery effort. Through the combined efforts of the USFWS field team and the RWRIT, the threat of introgression of coyote (Canis latrans) genes into the red wolf population has been substantially curtailed within the recovery area, and red wolf numbers and range have increased. The RWRIT serves as an example of a recovery implementation team that is successfully incorporating the principles of adaptive management and whose template could be adapted to other endangered species.