Interpolative multidimensional scaling techniques for the identification of clusters in very large sequence sets

<p>Abstract</p> <p>Background</p> <p>Modern pyrosequencing techniques make it possible to study complex bacterial populations, such as <it>16S rRNA</it>, directly from environmental or clinical samples without the need for laboratory purification. Alignment of sequences across the resultant large data sets (100,000+ sequences) is of particular interest for the purpose of identifying potential gene clusters and families, but such analysis represents a daunting computational task. The aim of this work is the development of an efficient pipeline for the clustering of large sequence read sets.</p> <p>Methods</p> <p>Pairwise alignment techniques are used here to calculate genetic distances between sequence pairs. These methods are pleasingly parallel and have been shown to more accurately reflect accurate genetic distances in highly variable regions of <it>rRNA </it>genes than do traditional multiple sequence alignment (MSA) approaches. By utilizing Needleman-Wunsch (NW) pairwise alignment in conjunction with novel implementations of interpolative multidimensional scaling (MDS), we have developed an effective method for visualizing massive biosequence data sets and quickly identifying potential gene clusters.</p> <p>Results</p> <p>This study demonstrates the use of interpolative MDS to obtain clustering results that are qualitatively similar to those obtained through full MDS, but with substantial cost savings. In particular, the wall clock time required to cluster a set of 100,000 sequences has been reduced from seven hours to less than one hour through the use of interpolative MDS.</p> <p>Conclusions</p> <p>Although work remains to be done in selecting the optimal training set size for interpolative MDS, substantial computational cost savings will allow us to cluster much larger sequence sets in the future.</p

The Significance of Repetitive Ventricular Responses Induced by Radiofrequency Energy Application for Idiopathic Left Ventricular Tachycardia

In radiofrequency (RF) ablation for idiopathic left ventricular tachycardia (ILVT), the termination of tachycardia during RF ablation is considered a hallmark of success. However, in cases of patients with difficulty of induction of ventricular tachycardia (VT), the evaluation of procedural success can be problematic. We have observed thermal responses reflected as ventricular rhythm change to RF energy delivered on sinus rhythm for ILVT. We therefore describe the significance of repetitive ventricular responses. The study subjects were 11 ILVT patients for whom RF energy was delivered during sinus rhythm because of difficulty in re-induction of tachycardia. During each energy delivery, we focused on the occurrence of repetitive ventricular responses especially exhibiting a similar morphology to clinical VT. The repetitive ventricular responses were noted in 10 of 11 patients. Two patients received a second procedure due to the recurrence of ILVT. The mean follow-up period was 36.2±12.8 months. The clinical course of the remaining patients was favorable and without recurrence of ILVT. Based on the favorable clinical outcomes, ablation-induced repetitive ventricular responses with similar QRS morphology to clinical ILVT are useful markers for selecting an ablation site and could be used as an additional mapping method, termed as "thermal mapping"

An inserted region of leucyl-tRNA synthetase plays a critical role in group I intron splicing

Yeast mitochondrial leucyl-tRNA synthetase (LeuRS) binds to the bI4 intron and collaborates with the bI4 maturase to aid excision of the group I intron. Deletion analysis isolated the inserted LeuRS CP1 domain as a critical factor in the protein’s splicing activity. Protein fragments comprised of just the LeuRS CP1 region rescued complementation of a yeast strain that expressed a splicing-defective LeuRS. Three-hybrid analysis determined that these CP1-containing LeuRS fragments, ranging from 214 to 375 amino acids, bound to the bI4 intron. In each case, interactions with only the LeuRS protein fragment specifically stimulated bI4 intron splicing activity. Substitution of a homologous CP1 domain from isoleucyl-tRNA synthetase or mutation within the LeuRS CP1 region of the smallest protein fragment abolished RNA binding and splicing activity. The CP1 domain is best known for its amino acid editing activity. However, these results suggest that elements within the LeuRS CP1 domain also play a novel role, independent of the full-length tRNA synthetase, in binding the bI4 group I intron and facilitating its self-splicing activity

A novel cervical cancer suppressor 3 (CCS-3) interacts with the BTB domain of PLZF and inhibits the cell growth by inducing apoptosis

AbstractPromyelocytic leukemia zinc finger protein (PLZF) is a sequence-specific, DNA binding, transcriptional repressor differentially expressed during embryogenesis and in adult tissues. PLZF is known to be a negative regulator of cell cycle progression. We used PLZF as bait in a yeast two-hybrid screen with a cDNA library from the human ovary tissue. A novel cervical cancer suppressor 3 (CCS-3) was identified as a PLZF interacting partner. Further characterization revealed the BTB domain as an interacting domain of PLZF. Interaction of CCS-3 with PLZF in mammalian cells was also confirmed by co-immunoprecipitation and in vitro binding assays. It was found that, although CCS-3 shares similar homology with eEF1A, the study determined CCS-3 to be an isoform. CCS-3 was observed to be downregulated in human cervical cell lines as well as in cervical tumors when compared to those from normal tissues. Overexpression of CCS-3 in human cervical cell lines inhibits cell growth by inducing apoptosis and suppressing human cyclin A2 promoter activity. These combined results suggest that the potential tumor suppressor activity of CCS-3 may be mediated by its interaction with PLZF