Significant speedup of database searches with HMMs by search space reduction with PSSM family models

Beckstette, Michael; Homann, Robert; Giegerich, Robert; Kurtz, Stefan

doi:10.1093/bioinformatics/btp593

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…Conserved sequence motifs were predicted by MEME (Bailey and Elkan, ) with a minimum size of 5 nucleotides, maximum size of 20 nucleotides, zero or one occurrence per sequence, using the promoter regions of eight GalA‐regulated genes as input. The occurrence of conserved motifs in the promoter regions of other genes was analysed with PoSSuM search (Beckstette et al ., ) by scanning for matches to the PSSMs describing the motif.…”

Section: Methodsmentioning

confidence: 99%

A novel Zn₂Cys₆ transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea

Zhang

Lubbers

Simon

et al. 2016

Molecular Microbiology

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D-galacturonic acid (GalA) is the most abundant monosaccharide component of pectin. Previous transcriptome analysis in the plant pathogenic fungus Botrytis cinerea identified eight GalA-inducible genes involved in pectin decomposition, GalA transport and utilization. Co-expression of these genes indicates that a specific regulatory mechanism occurs in B. cinerea. In this study, promoter regions of these genes were analysed and eight conserved sequence motifs identified. The Bclga1 promoter, containing all these motifs, was functionally analysed and the motif designated GalA Responsive Element (GARE) was identified as the crucial cis-regulatory element in regulation of GalA utilization in B. cinerea. Yeast one-hybrid screening with the GARE motif led to identification of a novel Zn2 Cys6 transcription factor (TF), designated BcGaaR. Targeted knockout analysis revealed that BcGaaR is required for induction of GalA-inducible genes and growth of B. cinerea on GalA. A BcGaaR-GFP fusion protein was predominantly localized in nuclei in mycelium grown in GalA. Fluorescence in nuclei was much stronger in mycelium grown in GalA, as compared to fructose and glucose. This study provides the first report of a GalA-specific TF in filamentous fungi. Orthologs of BcGaaR are present in other ascomycete fungi that are able to utilize GalA, including Aspergillus spp., Trichoderma reesei and Neurospora crassa.

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Section: Methodsmentioning

confidence: 99%

A novel Zn₂Cys₆ transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea

Zhang

Lubbers

Simon

et al. 2016

Molecular Microbiology

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“…We retrieved the gl_SOLEXA_5_FBgn0004618 binding site motif from Fly Factor Survey (Beckstette et al, 2009; Zhu et al, 2011). We used the motif to search the FlyBase r6.03 assembly for binding sites using PoSSumSearch2 with a p-value cutoff of 1E-04.…”

Section: Methodsmentioning

confidence: 99%

Two temporal functions of Glass: Ommatidium patterning and photoreceptor differentiation

Liang

Mahato

Hemmerich

et al. 2016

Developmental Biology

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Much progress has been made in elucidating the molecular networks required for specifying retinal cells, including photoreceptors, but the downstream mechanisms that maintain identity and regulate differentiation remain poorly understood. Here, we report that the transcription factor Glass has a dual role in establishing a functional Drosophila eye. Utilizing conditional rescue approaches, we confirm that persistent defects in ommatidium patterning combined with cell death correlate with the overall disruption of eye morphology in glass mutants. In addition, we reveal that Glass exhibits a separable role in regulating photoreceptor differentiation. In particular, we demonstrate the apparent loss of glass mutant photoreceptors is not only due to cell death but also a failure of the surviving photoreceptors to complete differentiation. Moreover, the late reintroduction of Glass in these developmentally stalled photoreceptors is capable of restoring differentiation in the absence of correct ommatidium patterning. Mechanistically, transcription profiling at the time of differentiation reveals that Glass is necessary for the expression of many genes implicated in differentiation, i.e. rhabdomere morphogenesis, phototransduction, and synaptogenesis. Specifically, we show Glass directly regulates the expression of Pph13, which encodes a transcription factor necessary for opsin expression and rhabdomere morphogenesis. Finally, we demonstrate the ability of Glass to choreograph photoreceptor differentiation is conserved between Drosophila and Tribolium, two holometabolous insects. Altogether, our work identifies a fundamental regulatory mechanism to generate the full complement of cells required for a functional rhabdomeric visual system and provides a critical framework to investigate the basis of differentiation and maintenance of photoreceptor identity.

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“…Locating reverse lcp-intervals can be accelerated by skp-tables. These tables, introduced in Beckstette et al [ 37 ] and hereinafter referred to as skp F and skp R , can be constructed in linear time [ 38 ] and allow one to quickly skip intervals in suf X (for details, see [ 37 ]).…”

Section: Methodsmentioning

confidence: 99%

Structator: fast index-based search for RNA sequence-structure patterns

et al. 2011

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BackgroundThe secondary structure of RNA molecules is intimately related to their function and often more conserved than the sequence. Hence, the important task of searching databases for RNAs requires to match sequence-structure patterns. Unfortunately, current tools for this task have, in the best case, a running time that is only linear in the size of sequence databases. Furthermore, established index data structures for fast sequence matching, like suffix trees or arrays, cannot benefit from the complementarity constraints introduced by the secondary structure of RNAs.ResultsWe present a novel method and readily applicable software for time efficient matching of RNA sequence-structure patterns in sequence databases. Our approach is based on affix arrays, a recently introduced index data structure, preprocessed from the target database. Affix arrays support bidirectional pattern search, which is required for efficiently handling the structural constraints of the pattern. Structural patterns like stem-loops can be matched inside out, such that the loop region is matched first and then the pairing bases on the boundaries are matched consecutively. This allows to exploit base pairing information for search space reduction and leads to an expected running time that is sublinear in the size of the sequence database. The incorporation of a new chaining approach in the search of RNA sequence-structure patterns enables the description of molecules folding into complex secondary structures with multiple ordered patterns. The chaining approach removes spurious matches from the set of intermediate results, in particular of patterns with little specificity. In benchmark experiments on the Rfam database, our method runs up to two orders of magnitude faster than previous methods.ConclusionsThe presented method's sublinear expected running time makes it well suited for RNA sequence-structure pattern matching in large sequence databases. RNA molecules containing several stem-loop substructures can be described by multiple sequence-structure patterns and their matches are efficiently handled by a novel chaining method. Beyond our algorithmic contributions, we provide with Structator a complete and robust open-source software solution for index-based search of RNA sequence-structure patterns. The Structator software is available at http://www.zbh.uni-hamburg.de/Structator.

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Significant speedup of database searches with HMMs by search space reduction with PSSM family models

Cited by 10 publications

References 42 publications

A novel Zn₂Cys₆ transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea

A novel Zn₂Cys₆ transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea

Two temporal functions of Glass: Ommatidium patterning and photoreceptor differentiation

Structator: fast index-based search for RNA sequence-structure patterns

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Significant speedup of database searches with HMMs by search space reduction with PSSM family models

Cited by 10 publications

References 42 publications

A novel Zn2Cys6 transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea

A novel Zn2Cys6 transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea

Two temporal functions of Glass: Ommatidium patterning and photoreceptor differentiation

Structator: fast index-based search for RNA sequence-structure patterns

Contact Info

Product

Resources

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A novel Zn₂Cys₆ transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea

A novel Zn₂Cys₆ transcription factor BcGaaR regulates D‐galacturonic acid utilization in Botrytis cinerea