RACS: Rapid Analysis of ChIP-Seq data for contig based genomes

Background: Chromatin immunoprecipitation coupled to next generation sequencing (ChIP-Seq) is a widely used technique to investigate the function of chromatin-related proteins in a genome-wide manner. ChIP-Seq generates large quantities of data which can be difficult to process and analyse, particularly for organisms with contig based genomes. Contig-based genomes often have poor annotations for cis-elements, for example enhancers, that are important for gene expression. Poorly annotated genomes make a comprehensive analysis of ChIP-Seq data difficult and as such standardized analysis pipelines are lacking. Methods: We report a computational pipeline that utilizes traditional High-Performance Computing techniques and open source tools for processing and analysing data obtained from ChIP-Seq. We applied our computational pipeline "Rapid Analysis of ChIP-Seq data" (RACS) to ChIP-Seq data that was generated in the model organism Tetrahymena thermophila, an example of an organism with a genome that is available in contigs. Results: To test the performance and efficiency of RACs, we performed control ChIP-Seq experiments allowing us to rapidly eliminate false positives when analyzing our previously published data set. Our pipeline segregates the found read accumulations between genic and intergenic regions and is highly efficient for rapid downstream analyses. Conclusions: Altogether, the computational pipeline presented in this report is an efficient and highly reliable tool to analyze genome-wide ChIP-Seq data generated in model organisms with contig-based genomes. RACS is an open source computational pipeline available to download from: https://bitbucket.org/mjponce/racs --or-- https://gitrepos.scinet.utoronto.ca/public/?a=summary&p=RACSComment: Submitted to BMC Bioinformatics. Computational pipeline available at https://bitbucket.org/mjponce/rac

Taking Care of Business in a Flash: Constraining the Timescale for Low-Mass Satellite Quenching with ELVIS

The vast majority of dwarf satellites orbiting the Milky Way and M31 are quenched, while comparable galaxies in the field are gas-rich and star-forming. Assuming that this dichotomy is driven by environmental quenching, we use the ELVIS suite of N-body simulations to constrain the characteristic timescale upon which satellites must quench following infall into the virial volumes of their hosts. The high satellite quenched fraction observed in the Local Group demands an extremely short quenching timescale (~ 2 Gyr) for dwarf satellites in the mass range Mstar ~ 10^6-10^8 Msun. This quenching timescale is significantly shorter than that required to explain the quenched fraction of more massive satellites (~ 8 Gyr), both in the Local Group and in more massive host halos, suggesting a dramatic change in the dominant satellite quenching mechanism at Mstar < 10^8 Msun. Combining our work with the results of complementary analyses in the literature, we conclude that the suppression of star formation in massive satellites (Mstar ~ 10^8 - 10^11 Msun) is broadly consistent with being driven by starvation, such that the satellite quenching timescale corresponds to the cold gas depletion time. Below a critical stellar mass scale of ~ 10^8 Msun, however, the required quenching times are much shorter than the expected cold gas depletion times. Instead, quenching must act on a timescale comparable to the dynamical time of the host halo. We posit that ram-pressure stripping can naturally explain this behavior, with the critical mass (of Mstar ~ 10^8 Msun) corresponding to halos with gravitational restoring forces that are too weak to overcome the drag force encountered when moving through an extended, hot circumgalactic medium.Comment: 12 pages, 6 figures; resubmitted to MNRAS after referee report (August 25, 2015

Under Pressure: Quenching Star Formation in Low-Mass Satellite Galaxies via Stripping

Recent studies of galaxies in the local Universe, including those in the Local Group, find that the efficiency of environmental (or satellite) quenching increases dramatically at satellite stellar masses below ~ $10^8\ {\rm M}_{\odot}$. This suggests a physical scale where quenching transitions from a slow "starvation" mode to a rapid "stripping" mode at low masses. We investigate the plausibility of this scenario using observed HI surface density profiles for a sample of 66 nearby galaxies as inputs to analytic calculations of ram-pressure and viscous stripping. Across a broad range of host properties, we find that stripping becomes increasingly effective at $M_{*} < 10^{8-9}\ {\rm M}_{\odot}$, reproducing the critical mass scale observed. However, for canonical values of the circumgalactic medium density ($n_{\rm halo} < 10^{-3.5}$${\rm cm}^{-3}$), we find that stripping is not fully effective; infalling satellites are, on average, stripped of < 40 - 70% of their cold gas reservoir, which is insufficient to match observations. By including a host halo gas distribution that is clumpy and therefore contains regions of higher density, we are able to reproduce the observed HI gas fractions (and thus the high quenched fraction and short quenching timescale) of Local Group satellites, suggesting that a host halo with clumpy gas may be crucial for quenching low-mass systems in Local Group-like (and more massive) host halos.Comment: updated version after review, now accepted to MNRAS; Accepted 2016 August 22. Received 2016 August 18; in original form 2016 June 2

Nucleus-specific linker histones Hho1 and Mlh1 form distinct protein interactions during growth, starvation and development in Tetrahymena thermophila

Chromatin organization influences most aspects of gene expression regulation. The linker histone H1, along with the core histones, is a key component of eukaryotic chromatin. Despite its critical roles in chromatin structure and function and gene regulation, studies regarding the H1 protein-protein interaction networks, particularly outside of Opisthokonts, are limited. The nuclear dimorphic ciliate protozoan Tetrahymena thermophila encodes two distinct nucleus-specific linker histones, macronuclear Hho1 and micronuclear Mlh1. We used a comparative proteomics approach to identify the Hho1 and Mlh1 protein-protein interaction networks in Tetrahymena during growth, starvation, and sexual development. Affinity purification followed by mass spectrometry analysis of the Hho1 and Mlh1 proteins revealed a non-overlapping set of co-purifying proteins suggesting that Tetrahymena nucleus-specific linker histones are subject to distinct regulatory pathways. Furthermore, we found that linker histones interact with distinct proteins under the different stages of the Tetrahymena life cycle. Hho1 and Mlh1 co-purified with several Tetrahymena-specific as well as conserved interacting partners involved in chromatin structure and function and other important cellular pathways. Our results suggest that nucleus-specific linker histones might be subject to nucleus-specific regulatory pathways and are dynamically regulated under different stages of the Tetrahymena life cycle.York University Librarie

The bromodomain-containing protein Ibd1 links multiple chromatin related protein complexes to highly expressed genes in Tetrahymena thermophila

Background: The chromatin remodelers of the SWI/SNF family are critical transcriptional regulators. Recognition of lysine acetylation through a bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes, this function is attributed to SNF2/Brg1. Results: Using affinity purification coupled to mass spectrometry (AP-MS) we identified members of a SWI/SNF complex (SWI/SNFTt) in Tetrahymena thermophila. SWI/SNFTt is composed of 11 proteins, Snf5Tt, Swi1Tt, Swi3Tt, Snf12Tt, Brg1Tt, two proteins with potential chromatin interacting domains and four proteins without orthologs to SWI/SNF proteins in yeast or mammals. SWI/SNFTt subunits localize exclusively to the transcriptionally active macronucleus (MAC) during growth and development, consistent with a role in transcription. While Tetrahymena Brg1 does not contain a BRD, our AP-MS results identified a BRD-containing SWI/SNFTt component, Ibd1 that associates with SWI/SNFTt during growth but not development. AP-MS analysis of epitope-tagged Ibd1 revealed it to be a subunit of several additional protein complexes, including putative SWRTt, and SAGATt complexes as well as a putative H3K4-specific histone methyl transferase complex. Recombinant Ibd1 recognizes acetyl-lysine marks on histones correlated with active transcription. Consistent with our AP-MS and histone array data suggesting a role in regulation of gene expression, ChIP-Seq analysis of Ibd1 indicated that it primarily binds near promoters and within gene bodies of highly expressed genes during growth. Conclusions: Our results suggest that through recognizing specific histones marks, Ibd1 targets active chromatin regions of highly expressed genes in Tetrahymena where it subsequently might coordinate the recruitment of several chromatin remodeling complexes to regulate the transcriptional landscape of vegetatively growing Tetrahymena cells.Comment: Published on BMC Epigenetics & Chromati

Environmental Quenching of Low-Mass Field Galaxies

In the local Universe, there is a strong division in the star-forming properties of low-mass galaxies, with star formation largely ubiquitous amongst the field population while satellite systems are predominantly quenched. This dichotomy implies that environmental processes play the dominant role in suppressing star formation within this low-mass regime (${M}_{\star} \sim 10^{5.5-8}~{\rm M}_{\odot}$). As shown by observations of the Local Volume, however, there is a non-negligible population of passive systems in the field, which challenges our understanding of quenching at low masses. By applying the satellite quenching models of Fillingham et al. (2015) to subhalo populations in the Exploring the Local Volume In Simulations (ELVIS) suite, we investigate the role of environmental processes in quenching star formation within the nearby field. Using model parameters that reproduce the satellite quenched fraction in the Local Group, we predict a quenched fraction -- due solely to environmental effects -- of $\sim 0.52 \pm 0.26$ within $1< R/R_{\rm vir} < 2$ of the Milky Way and M31. This is in good agreement with current observations of the Local Volume and suggests that the majority of the passive field systems observed at these distances are quenched via environmental mechanisms. Beyond $2~R_{\rm vir}$, however, dwarf galaxy quenching becomes difficult to explain through an interaction with either the Milky Way or M31, such that more isolated, field dwarfs may be self-quenched as a result of star-formation feedback.Comment: 9 pages, 4 figures, MNRAS accepted version, comments welcome - RIP Ducky...gone but never forgotte

The Evolution of Environmental Quenching Timescales to z∼1.6z\sim1.6

Using a sample of 4 galaxy clusters at $1.35 < z < 1.65$ and 10 galaxy clusters at $0.85 < z < 1.35$, we measure the environmental quenching timescale, $t_Q$, corresponding to the time required after a galaxy is accreted by a cluster for it to fully cease star formation. Cluster members are selected by a photometric-redshift criterion, and categorized as star-forming, quiescent, or intermediate according to their dust-corrected rest-frame colors and magnitudes. We employ a "delayed-then-rapid" quenching model that relates a simulated cluster mass accretion rate to the observed numbers of each type of galaxy in the cluster to constrain $t_Q$. For galaxies of mass $M_* \gtrsim 10^{10.5}~ \mathrm{M}_\odot$, we find a quenching timescale of $t_Q=$ 1.24 Gyr in the $z\sim1.5$ cluster sample, and $t_Q=$ 1.50 Gyr at $z\sim1$. Using values drawn from the literature, we compare the redshift evolution of $t_Q$ to timescales predicted for different physical quenching mechanisms. We find $t_Q$ to depend on host halo mass such that quenching occurs over faster timescales in clusters relative to groups, suggesting that properties of the host halo are responsible for quenching high-mass galaxies. Between $z=0$ and $z=1.5$, we find that $t_Q$ evolves faster than the molecular gas depletion timescale and slower than an SFR-outflow timescale, but is consistent with the evolution of the dynamical time. This suggests that environmental quenching in these galaxies is driven by the motion of satellites relative to the cluster environment, although due to uncertainties in the atomic gas budget at high redshift, we cannot rule out quenching due to simple gas depletion

Elective preterm birth for fetal gastroschisis (Review)

Background: Gastroschisis is an uncommon congenital defect of the interior abdominal wall that results in herniation of intestinal loops outside the abdominal cavity. Babies with gastroschisis generally do well, but there remains a mortality rate of 5% to 10% and some require prolonged parenteral nutrition and intensive care. Significant injury to the exposed bowel may occur in-utero, and earlier birth may reduce this, improve long-term outcomes and reduce complications, such as necrotising enterocolitis. However, it may also increase complications related to prematurity. There is a lack of published data in this area. Objectives: To assess the effects of elective preterm birth for fetal gastroschisis in pregnancies complicated by this condition. The mode of birth may be either vaginal or by caesarean section, but this review is studying only timing, not the route, of birth. Search methods: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (16 January 2013). Selection criteria: Individual patient randomised controlled trials of planned preterm birth in pregnancies complicated by fetal gastroschisis, diagnosed by ultrasound scanning in time for preterm birth to be an option, and without other fetal anomalies. The intervention is planned preterm birth, prior to 37 weeks and 0 days’ gestation, versus planned later birth, at or after 37 weeks and 0 days’ gestation (mode of birth is not part of the intervention). We did not include quasi-randomised controlled trials and cluster trials. Cross-over trials are not appropriate for this condition. Studies that were presented in abstract form only were eligible for inclusion, providing that the population included women with pregnancies affected by fetal gastroschisis, the interventions were defined and the treatment selection was randomised. Data collection and analysis: Two review authors independently assessed for inclusion the one trial identified as a result of the search strategy and assessed trial quality. Two review authors extracted data and checked it for accuracy. Main results: We included one study, involving 40 infants and 42 women. The trial was underpowered to detect clinically important outcome differences between the two policies. There were no significant benefits or adverse effects of elective preterm birth at 36 weeks’ gestation for fetal gastroschisis. The primary outcomes were caesarean section and neonatal survival to discharge. Two babies died after birth but before discharge in the elective (intervention) group versus none in the spontaneous group (risk ratio (RR) 5.00; 95% confidence interval (CI) 0.26 to 98.00; one study, n = 40). Seven women (33%) in the elective group and nine women (43%) in the spontaneous group delivered by caesarean section (RR 0.78; 95% CI 0.36 to 1.70). Similarly, for the secondary outcomes, there were no statistical differences in birthweight, ventilation requirements, necrotising enterocolitis and requirement for repeat surgery between the two groups. None of our prespecified maternal secondary outcomes were reported in the included study. We also examined gestational age at birth as a non-prespecified outcome. There was a difference in gestational age at birth between the two arms of the trial (35.8 weeks (SD 0.7) in the elective group and 36.7 (SD 1.5) in the spontaneous group. Possible reasons for this small mean difference include a trend towards spontaneous preterm birth in pregnancies complicated by fetal gastroschisis. Authors’ conclusions: This review is unable to draw any firm conclusions regarding pretermbirth for infants with gastroschisis. It is not possible to say whether the intervention is beneficial or harmful for these babies or their mothers. Only one small trial is included. Further research is needed in this area

DEVELOPING BETTER PARTNERSHIPS IN A FAMILY HEALTH TEAM

This organizational improvement plan (OIP) considers the experience of an Ontario family health team whose growing portfolio of partnerships requires evidence-based structure. A brief review of the literature suggests that partnerships are best understood as social constructs, shared spaces that are co-created through the multiple perspectives of their contributors. Synthesis of competing perspectives, integration, is a recurring theme throughout the OIP. Two well-known organizational change models are integrated to create a system change model (SCM) more applicable to the system-level change inherent to healthcare partnerships and this OIP. SCM is supported by an integrated approach to leadership, the incorporation of two leadership theories that value different types of relationships, one within systems (complexity), and the other between people (authentic). Four potential solutions are presented, and a preferred option identified: adopting and adapting a partnership framework for multi-sectoral collaboration by integrating Relational Coordination where communication and relationship-building could support task integration across partner organizations. A test of change partnership using one of the family health team’s most ambitious collaborations is identified, and a supporting change implementation plan described using the SCM framework. The OIP was authored during a time of significant transformation in Ontario’s healthcare system, sometimes giving the writing process the feel of field reporting. As such, it is likely that the healthcare landscape will change again, rendering the concepts of this OIP more applicable to the author’s practice than any specifics in the implementation plan