18,133 research outputs found
Entropy-scaling search of massive biological data
Many datasets exhibit a well-defined structure that can be exploited to
design faster search tools, but it is not always clear when such acceleration
is possible. Here, we introduce a framework for similarity search based on
characterizing a dataset's entropy and fractal dimension. We prove that
searching scales in time with metric entropy (number of covering hyperspheres),
if the fractal dimension of the dataset is low, and scales in space with the
sum of metric entropy and information-theoretic entropy (randomness of the
data). Using these ideas, we present accelerated versions of standard tools,
with no loss in specificity and little loss in sensitivity, for use in three
domains---high-throughput drug screening (Ammolite, 150x speedup), metagenomics
(MICA, 3.5x speedup of DIAMOND [3,700x BLASTX]), and protein structure search
(esFragBag, 10x speedup of FragBag). Our framework can be used to achieve
"compressive omics," and the general theory can be readily applied to data
science problems outside of biology.Comment: Including supplement: 41 pages, 6 figures, 4 tables, 1 bo
Compressing DNA sequence databases with coil
Background: Publicly available DNA sequence databases such as GenBank are large, and are
growing at an exponential rate. The sheer volume of data being dealt with presents serious storage
and data communications problems. Currently, sequence data is usually kept in large "flat files,"
which are then compressed using standard Lempel-Ziv (gzip) compression – an approach which
rarely achieves good compression ratios. While much research has been done on compressing
individual DNA sequences, surprisingly little has focused on the compression of entire databases
of such sequences. In this study we introduce the sequence database compression software coil.
Results: We have designed and implemented a portable software package, coil, for compressing
and decompressing DNA sequence databases based on the idea of edit-tree coding. coil is geared
towards achieving high compression ratios at the expense of execution time and memory usage
during compression – the compression time represents a "one-off investment" whose cost is
quickly amortised if the resulting compressed file is transmitted many times. Decompression
requires little memory and is extremely fast. We demonstrate a 5% improvement in compression
ratio over state-of-the-art general-purpose compression tools for a large GenBank database file
containing Expressed Sequence Tag (EST) data. Finally, coil can efficiently encode incremental
additions to a sequence database.
Conclusion: coil presents a compelling alternative to conventional compression of flat files for the
storage and distribution of DNA sequence databases having a narrow distribution of sequence
lengths, such as EST data. Increasing compression levels for databases having a wide distribution of
sequence lengths is a direction for future work
Improving average ranking precision in user searches for biomedical research datasets
Availability of research datasets is keystone for health and life science
study reproducibility and scientific progress. Due to the heterogeneity and
complexity of these data, a main challenge to be overcome by research data
management systems is to provide users with the best answers for their search
queries. In the context of the 2016 bioCADDIE Dataset Retrieval Challenge, we
investigate a novel ranking pipeline to improve the search of datasets used in
biomedical experiments. Our system comprises a query expansion model based on
word embeddings, a similarity measure algorithm that takes into consideration
the relevance of the query terms, and a dataset categorisation method that
boosts the rank of datasets matching query constraints. The system was
evaluated using a corpus with 800k datasets and 21 annotated user queries. Our
system provides competitive results when compared to the other challenge
participants. In the official run, it achieved the highest infAP among the
participants, being +22.3% higher than the median infAP of the participant's
best submissions. Overall, it is ranked at top 2 if an aggregated metric using
the best official measures per participant is considered. The query expansion
method showed positive impact on the system's performance increasing our
baseline up to +5.0% and +3.4% for the infAP and infNDCG metrics, respectively.
Our similarity measure algorithm seems to be robust, in particular compared to
Divergence From Randomness framework, having smaller performance variations
under different training conditions. Finally, the result categorization did not
have significant impact on the system's performance. We believe that our
solution could be used to enhance biomedical dataset management systems. In
particular, the use of data driven query expansion methods could be an
alternative to the complexity of biomedical terminologies
Multi-membership gene regulation in pathway based microarray analysis
This article is available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. Results: We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. Conclusions: We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes.The work was sponsored by the studentship scheme of the School of Information Systems, Computing and Mathematics, Brunel Universit
Species-level functional profiling of metagenomes and metatranscriptomes.
Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types
Transcriptomic analysis of the entomopathogenic nematode Heterorhabditis bacteriophora TTO1
Background:
The entomopathogenic nematode Heterorhabditis bacteriophora and its symbiotic bacterium, Photorhabdus luminescens, are important biological control agents of insect pests. This nematode-bacterium-insect association represents an emerging tripartite model for research on mutualistic and parasitic symbioses. Elucidation of mechanisms underlying these biological processes may serve as a foundation for improving the biological control potential of the nematode-bacterium complex. This large-scale expressed sequence tag (EST) analysis effort enables gene discovery and development of microsatellite markers. These ESTs will also aid in the annotation of the upcoming complete genome sequence of H. bacteriophora.
Results:
A total of 31,485 high quality ESTs were generated from cDNA libraries of the adult H. bacteriophora TTO1 strain. Cluster analysis revealed the presence of 3,051 contigs and 7,835 singletons, representing 10,886 distinct EST sequences. About 72% of the distinct EST sequences had significant matches (E value < 1e-5) to proteins in GenBank's non-redundant (nr) and Wormpep190 databases. We have identified 12 ESTs corresponding to 8 genes potentially involved in RNA interference, 22 ESTs corresponding to 14 genes potentially involved in dauer-related processes, and 51 ESTs corresponding to 27 genes potentially involved in defense and stress responses. Comparison to ESTs and proteins of free-living nematodes led to the identification of 554 parasitic nematode-specific ESTs in H. bacteriophora, among which are those encoding F-box-like/WD-repeat protein theromacin, Bax inhibitor-1-like protein, and PAZ domain containing protein. Gene Ontology terms were assigned to 6,685 of the 10,886 ESTs. A total of 168 microsatellite loci were identified with primers designable for 141 loci.
Conclusion:
A total of 10,886 distinct EST sequences were identified from adult H. bacteriophora cDNA libraries. BLAST searches revealed ESTs potentially involved in parasitism, RNA interference, defense responses, stress responses, and dauer-related processes. The putative microsatellite markers identified in H. bacteriophora ESTs will enable genetic mapping and population genetic studies. These genomic resources provide the material base necessary for genome annotation, microarray development, and in-depth gene functional analysis
Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi
DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi
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