26,033 research outputs found
Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality
Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis and mirror adaptive CD4(+) T helper (Th) cell subtypes in both usage of effector molecules and transcription factors. To better understand the relationship between ILC subsets and their Th cell counterparts, we measured genome-wide chromatin accessibility. We find that chromatin in proximity to effector genes is selectively accessible in ILCs prior to high-level transcription upon activation. Accessibility of these regions is acquired in a stepwise manner during development and changes little after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurs in naive CD4(+) T cells during Th cell differentiation using a type-2-infection model. This alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our data indicate extensive sharing of regulatory circuitry across the innate and adaptive compartments of the immune system, in spite of their divergent developing pathways
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Systems and methods for physiological signal enhancement and biometric extraction using non-invasive optical sensors
A system and method for signal processing to remove unwanted noise components including: (i) wavelength-independent motion artifacts such as tissue, bone and skin effects, and (ii) wavelength-dependent motion artifact/noise components such as venous blood pulsation and movement due to various sources including muscle pump, respiratory pump and physical perturbation. Disclosed are methods, analytics, and their uses for reliable perfusion monitoring, arterial oxygen saturation monitoring, heart rate monitoring during daily activities and in hospital settings and for extraction of physiological parameters such as respiration information, hemodynamic parameters, venous capacity, and fluid responsiveness. The system and methods disclosed are extendable to include monitoring platforms for perfusion, hypoxia, arrhythmia detection, airway obstruction detection and sleep disorders including apnea.Board of Regents, University of Texas Syste
Formation of regulatory modules by local sequence duplication
Turnover of regulatory sequence and function is an important part of
molecular evolution. But what are the modes of sequence evolution leading to
rapid formation and loss of regulatory sites? Here, we show that a large
fraction of neighboring transcription factor binding sites in the fly genome
have formed from a common sequence origin by local duplications. This mode of
evolution is found to produce regulatory information: duplications can seed new
sites in the neighborhood of existing sites. Duplicate seeds evolve
subsequently by point mutations, often towards binding a different factor than
their ancestral neighbor sites. These results are based on a statistical
analysis of 346 cis-regulatory modules in the Drosophila melanogaster genome,
and a comparison set of intergenic regulatory sequence in Saccharomyces
cerevisiae. In fly regulatory modules, pairs of binding sites show
significantly enhanced sequence similarity up to distances of about 50 bp. We
analyze these data in terms of an evolutionary model with two distinct modes of
site formation: (i) evolution from independent sequence origin and (ii)
divergent evolution following duplication of a common ancestor sequence. Our
results suggest that pervasive formation of binding sites by local sequence
duplications distinguishes the complex regulatory architecture of higher
eukaryotes from the simpler architecture of unicellular organisms
IIR Adaptive Filters for Detection of Gravitational Waves from Coalescing Binaries
In this paper we propose a new strategy for gravitational waves detection
from coalescing binaries, using IIR Adaptive Line Enhancer (ALE) filters. This
strategy is a classical hierarchical strategy in which the ALE filters have the
role of triggers, used to select data chunks which may contain gravitational
events, to be further analyzed with more refined optimal techniques, like the
the classical Matched Filter Technique. After a direct comparison of the
performances of ALE filters with the Wiener-Komolgoroff optimum filters
(matched filters), necessary to discuss their performance and to evaluate the
statistical limitation in their use as triggers, we performed a series of
tests, demonstrating that these filters are quite promising both for the
relatively small computational power needed and for the robustness of the
algorithms used. The performed tests have shown a weak point of ALE filters,
that we fixed by introducing a further strategy, based on a dynamic bank of ALE
filters, running simultaneously, but started after fixed delay times. The
results of this global trigger strategy seems to be very promising, and can be
already used in the present interferometers, since it has the great advantage
of requiring a quite small computational power and can easily run in real-time,
in parallel with other data analysis algorithms.Comment: Accepted at SPIE: "Astronomical Telescopes and Instrumentation". 9
pages, 3 figure
Response to comment on "Human-specific gain of function in a developmental enhancer"
Duret and Galtier argue that human-specific sequence divergence and gain of function in the HACNS1 enhancer result from deleterious biased gene conversion (BGC) with no contribution from positive selection. We reinforce our previous conclusion by analyzing hypothesized BGC
events genomewide and assessing the effect of recombination rates on human-accelerated conserved noncoding sequence ascertainment. We also provide evidence that AT → GC substitution bias can coexist with positive selection
Iterative Random Forests to detect predictive and stable high-order interactions
Genomics has revolutionized biology, enabling the interrogation of whole
transcriptomes, genome-wide binding sites for proteins, and many other
molecular processes. However, individual genomic assays measure elements that
interact in vivo as components of larger molecular machines. Understanding how
these high-order interactions drive gene expression presents a substantial
statistical challenge. Building on Random Forests (RF), Random Intersection
Trees (RITs), and through extensive, biologically inspired simulations, we
developed the iterative Random Forest algorithm (iRF). iRF trains a
feature-weighted ensemble of decision trees to detect stable, high-order
interactions with same order of computational cost as RF. We demonstrate the
utility of iRF for high-order interaction discovery in two prediction problems:
enhancer activity in the early Drosophila embryo and alternative splicing of
primary transcripts in human derived cell lines. In Drosophila, among the 20
pairwise transcription factor interactions iRF identifies as stable (returned
in more than half of bootstrap replicates), 80% have been previously reported
as physical interactions. Moreover, novel third-order interactions, e.g.
between Zelda (Zld), Giant (Gt), and Twist (Twi), suggest high-order
relationships that are candidates for follow-up experiments. In human-derived
cells, iRF re-discovered a central role of H3K36me3 in chromatin-mediated
splicing regulation, and identified novel 5th and 6th order interactions,
indicative of multi-valent nucleosomes with specific roles in splicing
regulation. By decoupling the order of interactions from the computational cost
of identification, iRF opens new avenues of inquiry into the molecular
mechanisms underlying genome biology
Genome Assembly Improvement and Mapping Convergently Evolved Skeletal Traits in Sticklebacks with Genotyping-by-Sequencing.
Marine populations of the threespine stickleback (Gasterosteus aculeatus) have repeatedly colonized and rapidly adapted to freshwater habitats, providing a powerful system to map the genetic architecture of evolved traits. Here, we developed and applied a binned genotyping-by-sequencing (GBS) method to build dense genome-wide linkage maps of sticklebacks using two large marine by freshwater F2 crosses of more than 350 fish each. The resulting linkage maps significantly improve the genome assembly by anchoring 78 new scaffolds to chromosomes, reorienting 40 scaffolds, and rearranging scaffolds in 4 locations. In the revised genome assembly, 94.6% of the assembly was anchored to a chromosome. To assess linkage map quality, we mapped quantitative trait loci (QTL) controlling lateral plate number, which mapped as expected to a 200-kb genomic region containing Ectodysplasin, as well as a chromosome 7 QTL overlapping a previously identified modifier QTL. Finally, we mapped eight QTL controlling convergently evolved reductions in gill raker length in the two crosses, which revealed that this classic adaptive trait has a surprisingly modular and nonparallel genetic basis
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