Evolution of sex-biased expression in Caenorhabditis

Mating systems have a profound impact on genome structure evolution, both indirectly through their effects on population genetics and directly due to the genetic control of reproductive traits. Most extant Caenorhabditis species are gonochoristic (males and females), while the most studied species, C. elegans and C. briggsae, are androdioecious (self-fertile hermaphrodites and males). The latter two species display an overall reduced ability to mate, suggesting that the selective pressure on maintaining efficient mating was weakened as selfing arose. The genes underlying these traits were likely to have been expressed in a sex-biased fashion in the gonochoristic ancestor, and we hypothesized that as selfing emerged their regulation was modified or they were lost altogether. This hypothesis is especially interesting given that selfing species have consistently smaller genome sizes than their gonochoristic relatives. I sought to address whether a disproportionate loss of genes with sex-biased expression accompanies the loss of mating-related traits in Caenorhabditis hermaphrodites. I first examine sex-biased expression in a gonochoristic species, C. remanei, and identify genes with highly sex-biased expression. I find that these genes are more likely to be missing in selfing species than expected by chance. I then select some of these genes based on their phylogenetic conservation patterns in the genus, and characterize them more thoroughly to shed some light on their functions. Through this study I identify a novel male-associated candidate cis-regulatory element. Lastly, I broaden the scope of the study by determining transcriptome wide sex-biased expression patterns in four Caenorhabditis species. I confirm that C.elegans displays a decrease in the proportion of strong female-biased expression, as well as a modification of the expression of genes with male-biased expression both in males and in hermaphrodites, when compared to gonochoristic Caenorhabditis. Taken together, this study illustrates the transcriptomic consequences of a modification of the mating system, and begins to address its effect on genome structure

Computing Delay-Constrained Least-Cost Paths for Segment Routing is Easier Than You Think

With the growth of demands for quasi-instantaneous communication services such as real-time video streaming, cloud gaming, and industry 4.0 applications, multi-constraint Traffic Engineering (TE) becomes increasingly important. While legacy TE management planes have proven laborious to deploy, Segment Routing (SR) drastically eases the deployment of TE paths and thus became the most appropriate technology for many operators. The flexibility of SR sparked demands in ways to compute more elaborate paths. In particular, there exists a clear need in computing and deploying Delay-Constrained Least-Cost paths (DCLC) for real-time applications requiring both low delay and high bandwidth routes. However, most current DCLC solutions are heuristics not specifically tailored for SR. In this work, we leverage both inherent limitations in the accuracy of delay measurements and an operational constraint added by SR. We include these characteristics in the design of BEST2COP, an exact but efficient ECMP-aware algorithm that natively solves DCLC in SR domains. Through an extensive performance evaluation, we first show that BEST2COP scales well even in large random networks. In real networks having up to thousands of destinations, our algorithm returns all DCLC solutions encoded as SR paths in way less than a second

Detecting heterozygosity in shotgun genome assemblies: Lessons from obligately outcrossing nematodes

The majority of nematodes are gonochoristic (dioecious) with distinct male and female sexes, but the best-studied species, Caenorhabditis elegans, is a self-fertile hermaphrodite. The sequencing of the genomes of C. elegans and a second hermaphrodite, C. briggsae, was facilitated in part by the low amount of natural heterozygosity, which typifies selfing species. Ongoing genome projects for gonochoristic Caenorhabditis species seek to approximate this condition by intense inbreeding prior to sequencing. Here we show that despite this inbreeding, the heterozygous fraction of the whole genome shotgun assemblies of three gonochoristic Caenorhabditis species, C. brenneri, C. remanei, and C. japonica, is considerable. We first demonstrate experimentally that independently assembled sequence variants in C. remanei and C. brenneri are allelic. We then present gene-based approaches for recognizing heterozygous regions of WGS assemblies. We also develop a simple method for quantifying heterozygosity that can be applied to assemblies lacking gene annotations. Consistently we find that ∼10% and 30% of the C. remanei and C. brenneri genomes, respectively, are represented by two alleles in the assemblies. Heterozygosity is restricted to autosomes and its retention is accompanied by substantial inbreeding depression, suggesting that it is caused by multiple recessive deleterious alleles and not merely by chance. Both the overall amount and chromosomal distribution of heterozygous DNA is highly variable between assemblies of close relatives produced by identical methodologies, and allele frequencies have continued to change after strains were sequenced. Our results highlight the impact of mating systems on genome sequencing projects

ImmPort, toward repurposing of open access immunological assay data for translational and clinical research

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components–Private Data, Shared Data, Data Analysis, and Resources—for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the ImmPort Shared Data portal , which allows research data to be repurposed to accelerate the translation of new insights into discoveries

Outcome after heart-lung or lung transplantation in patients with Eisenmenger syndrome

Objective The optimal timing for transplantation is unclear in patients with Eisenmenger syndrome (ES). We investigated post-transplantation survival and transplantation-specific morbidity after heart-lung transplantation (HLTx) or lung transplantation (LTx) in a cohort of Nordic patients with ES to aid decision-making for scheduling transplantation. Methods We performed a retrospective, descriptive, population-based study of patients with ES who underwent transplantation from 1985 to 2012. Results Among 714 patients with ES in the Nordic region, 63 (9%) underwent transplantation. The median age at transplantation was 31.9 (IQR 21.1-42.3) years. Within 30 days after transplantation, seven patients (11%) died. The median survival was 12.0 (95% CI 7.6 to 16.4) years and the overall 1-year, 5-year, 10-year and 15-year survival rates were 84.1%, 69.7%, 55.8% and 40.6%, respectively. For patients alive 1 year post-transplantation, the median conditional survival was 14.8 years (95% CI 8.0 to 21.8), with 5-year, 10-year and 15-year survival rates of 83.3%, 67.2% and 50.0%, respectively. There was no difference in median survival after HLTx (n=57) and LTx (n=6) (14.9 vs 10.6 years, p=0.718). Median cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis/kidney transplantation-free survival rates were 11.2 (95% CI 7.8 to 14.6), 6.9 (95% CI 2.6 to 11.1) and 11.2 (95% CI 8.8 to 13.7) years, respectively. The leading causes of death after the perioperative period were infection (36.7%), bronchiolitis obliterans syndrome (23.3%) and heart failure (13.3%). Conclusions This study shows that satisfactory post-transplantation survival, comparable with contemporary HTx and LTx data, without severe comorbidities such as cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis, is achievable in patients with ES, with a conditional survival of nearly 15 years.Peer reviewe

Enabling precision medicine in neonatology, an integrated repository for preterm birth research.

Preterm birth, or the delivery of an infant prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. In the last decade, the advent and continued development of molecular profiling technologies has enabled researchers to generate vast amount of 'omics' data, which together with integrative computational approaches, can help refine the current knowledge about disease mechanisms, diagnostics, and therapeutics. Here we describe the March of Dimes' Database for Preterm Birth Research (http://www.immport.org/resources/mod), a unique resource that contains a variety of 'omics' datasets related to preterm birth. The database is open publicly, and as of January 2018, links 13 molecular studies with data across tens of thousands of patients from 6 measurement modalities. The data in the repository are highly diverse and include genomic, transcriptomic, immunological, and microbiome data. Relevant datasets are augmented with additional molecular characterizations of almost 25,000 biological samples from public databases. We believe our data-sharing efforts will lead to enhanced research collaborations and coordination accelerating the overall pace of discovery in preterm birth research

MetaCyto: A Tool for Automated Meta-analysis of Mass and Flow Cytometry Data

While meta-analysis has demonstrated increased statistical power and more robust estimations in studies, the application of this commonly accepted methodology to cytometry data has been challenging. Different cytometry studies often involve diverse sets of markers. Moreover, the detected values of the same marker are inconsistent between studies due to different experimental designs and cytometer configurations. As a result, the cell subsets identified by existing auto-gating methods cannot be directly compared across studies. We developed MetaCyto for automated meta-analysis of both flow and mass cytometry (CyTOF) data. By combining clustering methods with a silhouette scanning method, MetaCyto is able to identify commonly labeled cell subsets across studies, thus enabling meta-analysis. Applying MetaCyto across a set of ten heterogeneous cytometry studies totaling 2,926 samples enabled us to identify multiple cell populations exhibiting differences in abundance between demographic groups

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Internet Science Moonshot: Expanding BGP Data Horizons

Dramatic growth in Internet connectivity poses a challenge for the resource-constrained data collection efforts that sup- port scientific and operational analysis of interdomain rout- ing. Inspired by tradeoffs made in other disciplines, we ex- plore a fundamental reconceptualization to how we design public BGP data collection architectures: an overshoot-and- discard approach that can accommodate an order of magni- tude increase in vantage points by discarding redundant data shortly after its collection. As defining redundant depends on the context, we design algorithms that filter redundant updates without optimizing for one objective, and evaluate our approach in terms of detecting two noteworthy phenom- ena using BGP data: AS-topology mapping and hijacks. Our approach can generalize to other types of Internet data (e.g., traceroute, traffic). We offer this study as a first step to a potentially new area of Internet measurement research