Sorting and Selection in Posets

Classical problems of sorting and searching assume an underlying linear ordering of the objects being compared. In this paper, we study these problems in the context of partially ordered sets, in which some pairs of objects are incomparable. This generalization is interesting from a combinatorial perspective, and it has immediate applications in ranking scenarios where there is no underlying linear ordering, e.g., conference submissions. It also has applications in reconstructing certain types of networks, including biological networks. Our results represent significant progress over previous results from two decades ago by Faigle and Turán. In particular, we present the first algorithm that sorts a width-w poset of size n with query complexity O(n(w+\log n)) and prove that this query complexity is asymptotically optimal. We also describe a variant of Mergesort with query complexity O(wn log n/w) and total complexity O(w2n log n/w); an algorithm with the same query complexity was given by Faigle and Turán, but no efficient implementation of that algorithm is known. Both our sorting algorithms can be applied with negligible overhead to the more general problem of reconstructing transitive relations. We also consider two related problems: finding the minimal elements, and its generalization to finding the bottom k “levels,” called the k-selection problem. We give efficient deterministic and randomized algorithms for finding the minimal elements with query complexity and total complexity O(wn). We provide matching lower bounds for the query complexity up to a factor of 2 and generalize the results to the k-selection problem. Finally, we present efficient algorithms for computing a linear extension of a poset and computing the heights of all elements

PhylOTU: a high-throughput procedure quantifies microbial community diversity and resolves novel taxa from metagenomic data.

Microbial diversity is typically characterized by clustering ribosomal RNA (SSU-rRNA) sequences into operational taxonomic units (OTUs). Targeted sequencing of environmental SSU-rRNA markers via PCR may fail to detect OTUs due to biases in priming and amplification. Analysis of shotgun sequenced environmental DNA, known as metagenomics, avoids amplification bias but generates fragmentary, non-overlapping sequence reads that cannot be clustered by existing OTU-finding methods. To circumvent these limitations, we developed PhylOTU, a computational workflow that identifies OTUs from metagenomic SSU-rRNA sequence data through the use of phylogenetic principles and probabilistic sequence profiles. Using simulated metagenomic data, we quantified the accuracy with which PhylOTU clusters reads into OTUs. Comparisons of PCR and shotgun sequenced SSU-rRNA markers derived from the global open ocean revealed that while PCR libraries identify more OTUs per sequenced residue, metagenomic libraries recover a greater taxonomic diversity of OTUs. In addition, we discover novel species, genera and families in the metagenomic libraries, including OTUs from phyla missed by analysis of PCR sequences. Taken together, these results suggest that PhylOTU enables characterization of part of the biosphere currently hidden from PCR-based surveys of diversity

GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology

There is growing recognition that regionalization of bacterial colonization and immunity along the intestinal tract has an important role in health and disease. Yet, the mechanisms underlying intestinal regionalization and its dysregulation in disease are not well understood. This study found that regional epithelial expression of the transcription factor GATA4 controls bacterial colonization and inflammatory tissue immunity in the proximal small intestine by regulating retinol metabolism and luminal IgA. Furthermore, in mice without jejunal GATA4 expression, the commensal segmented filamentous bacteria promoted pathogenic inflammatory immune responses that disrupted barrier function and increased mortality upon Citrobacter rodentium infection. In celiac disease patients, low GATA4 expression was associated with metabolic alterations, mucosal Actinobacillus, and increased IL-17 immunity. Taken together, these results reveal broad impacts of GATA4-regulated intestinal regionalization on bacterial colonization and tissue immunity, highlighting an elaborate interdependence of intestinal metabolism, immunity, and microbiota in homeostasis and disease.</p

The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation

Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes. The neuropeptide receptor Nmur1 was preferentially expressed by ILC2s at steady state and after IL-25 stimulation. Neuromedin U (NMU), the ligand of NMUR1, activated ILC2s in vitro, and in vivo co-administration of NMU with IL-25 strongly amplified allergic inflammation. Loss of NMU-NMUR1 signalling reduced ILC2 frequency and effector function, and altered transcriptional programs following allergen challenge in vivo. Thus, NMUR1 signalling promotes inflammatory ILC2 responses, highlighting the importance of neuro-immune crosstalk in allergic inflammation at mucosal surfaces

Beyond classification: gene-family phylogenies from shotgun metagenomic reads enable accurate community analysis

Abstract Background Sequence-based phylogenetic trees are a well-established tool for characterizing diversity of both macroorganisms and microorganisms. Phylogenetic methods have recently been applied to shotgun metagenomic data from microbial communities, particularly with the aim of classifying reads. But the accuracy of gene-family phylogenies that characterize evolutionary relationships among short, non-overlapping sequencing reads has not been thoroughly evaluated. Results To quantify errors in metagenomic read trees, we developed MetaPASSAGE, a software pipeline to generate in silico bacterial communities, simulate a sample of shotgun reads from a gene family represented in the community, orient or translate reads, and produce a profile-based alignment of the reads from which a gene-family phylogenetic tree can be built. We applied MetaPASSAGE to a variety of RNA and protein-coding gene families, built trees using a range of different phylogenetic methods, and compared the resulting trees using topological and branch-length error metrics. We identified read length as one of the major sources of error. Because phylogenetic methods use a reference database of full-length sequences from the gene family to guide construction of alignments and trees, we found that error can also be substantially reduced through increasing the size and diversity of the reference database. Finally, UniFrac analysis, which compares metagenomic samples based on a summary statistic computed over all branches in a read tree, is very robust to the level of error we observe. Conclusions Bacterial community diversity can be quantified using phylogenetic approaches applied to shotgun metagenomic data. As sequencing reads get longer and more genomes across the bacterial tree of life are sequenced, the accuracy of this approach will continue to improve, opening the door to more applications

Genomics through the lens of next-generation sequencing.

A report on the 23rd annual meeting on 'The Biology of Genomes', 11-15 May 2010, Cold Spring Harbor, USA

Genomics through the lens of next-generation sequencing

A report on the 23rd annual meeting on 'The Biology of Genomes', 11-15 May 2010, Cold Spring Harbor, USA. MEETING REPORT: Recent advances in high-throughput sequencing technologies have greatly increased the scale and scope of genomics research, and this was evident throughout the recent Biology of Genomes meeting at the Cold Spring Harbor Laboratory. Here we describe some highlights of the meeting