Centromeres: long intergenic spaces with adaptive features

Centromeres are composed of inner kinetochore proteins, which are largely conserved across species, and repetitive DNA, which shows comparatively little sequence conservation. Due to this fundamental paradox the formation and maintenance of centromeres remains largely a mystery. However, it has become increasingly clear that a long-standing balance between epigenetic and genetic control governs the interactions of centromeric DNA and inner kinetochore proteins. The comparison of classical neocentromeres in plants, which are entirely genetic in their mode of operation, and clinical neocentromeres, which are sequence-independent, illustrates the conflict between genetics and epigenetics in regions that control their own transmission to progeny. Tandem repeat arrays present in centromeres may have an origin in meiotic drive or other selfish patterns of evolution, as is the case for the CENP-B box and CENP-B protein in human. In grasses retrotransposons have invaded centromeres to the point of complete domination, consequently breaking genetic regulation at these centromeres. The accumulation of tandem repeats and transposons causes centromeres to expand in size, effectively pushing genes to the sides and opening the centromere to ever fewer constraints on the DNA sequence. On genetic maps centromeres appear as long intergenic spaces that evolve rapidly and apparently without regard to host fitness.     

DNA array with the groESL intergenic sequence to detect Vibrio parahaemolyticus and Vibrio vulnificus

The untranscribed DNA sequences of the intergenic spacer regions (ISRs) in the groESL gene of 23 Vibrio species were determined and compared. ISR sequence length (41-85 bp) was variable. Vibrio species could be divided into three groups according to the length and homology of their ISR sequences. DNA array hybridization using ISR-specific probes accurately distinguished Vibrio parahaemolyticus and Vibrio vulnificus from other species.     

Predicting stable functional peptides from the intergenic space of E. coli

Expression of synthetic proteins from intergenic regions of E. coli and their functional association was recently demonstrated (Dhar et al. in J Biol Eng 3:2, 2009. doi:10.1186/1754-1611-3-2). This gave birth to the question: if one can make ‘user-defined’ genes from non-coding genome—how big is the artificially translatable genome? (Dinger et al. in PLoS Comput Biol 4, 2008; Frith et al. in RNA Biol 3(1):40–48, 2006a; Frith et al. in PLoS Genet 2(4):e52, 2006b). To answer this question, we performed a bioinformatics study of all reported E. coli intergenic sequences, in search of novel peptides and proteins, unexpressed by nature. Overall, 2500 E. coli intergenic sequences were computationally translated into ‘protein sequence equivalents’ and matched against all known proteins. Sequences that did not show any resemblance were used for building a comprehensive profile in terms of their structure, function, localization, interactions, stability so on. A total of 362 protein sequences showed evidence of stable tertiary conformations encoded by the intergenic sequences of E. coli genome. Experimental studies are underway to confirm some of the key predictions. This study points to a vast untapped repository of functional molecules lying undiscovered in the non-expressed genome of various organisms.     

A technique for using hair tubes beneath the snowpack to detect winter-active small mammals in the subnivean space

The study of winter-active small mammals beneath the snowpack has proved challenging for researchers because of the relative inaccessibility. We present a technique using hair tubes that permits the detection of small mammals active in the subnivean space. Hair tubes are cylindrical or funnel-shaped structures containing suitable bait and an adhesive surface that harvests hairs from small mammals as they attempt to reach the bait. Hair tubes eliminate many of the difficulties often associated with live trapping and permit the expansion of systematic sampling to larger scales than allowed by conventional live-trapping methods. The technique was used successfully to detect five small mammal species in the subnivean space in Kosciuszko National Park (KNP) in southeastern Australia. These included the common bush-rat, Rattus fuscipes; the dusky and agile antechinus, Antechinus swainsonii and A. agilis; the broad-toothed rat, Mastacomys fuscus; and the mountain pygmy possum, Burramys parvus. Although hair tubes have a number of limitations, such as not providing a measure of abundance or allowing the identification of individual animals, we believe that these limitations are balanced by the fact that the technique can be used at any spatial scale. Hair tubes are particularly suited to studies of animal distribution at the landscape-scale, because many hair tubes can be deployed and dispersed over large areas, and monitored on a regular basis by a small team of researchers. The technique also makes use of readily available, low-cost materials and could be easily adapted to a range of conditions and different target species.     

A method to detect proteinase activity using unprocessed X-ray films.

Routine assays to detect proteinases in biological samples are generally tedious and time-consuming. To expedite the recognition of proteinases, we have developed an assay utilizing the gelatin on the surface of an unprocessed Kodak X-Omat AR film as the proteolytic substrate. A positive reaction is indicated by a clear zone on the film after it has been rinsed with running water. This proteinase assay has been found to be inexpensive, rapid, and simple. Besides its ease of use, this assay has been found to be quantitatively reproducible with a well-defined endpoint. More importantly, this assay method is applicable to a variety of proteolytic enzymes under diverse pH (5-8.5) and salt conditions (up to 5 M NaCl) and has a sensitivity similar to that of azocoll. Since the assay does not require sophisticated equipment, it is useful as a general laboratory procedure.     

A method to detect enteroviruses in sewage sludge-amended soil using the PCR.

PCR detection of seeded poliovirus type 1 in sludge-amended soil was made possible by utilizing Sephadex G-50 and Chelex-100 resins to remove compounds present in sludge-amended soil that may inhibit PCR. With this method, enteroviruses indigenous to an anerobically digested sludge were detected by PCR in 10 different soils amended with this sludge.     

Rapid assay to detect peptidases in column effluent fractions using L-amino acid oxidase.

A rapid, sensitive method to detect peptidase activity which utilizes an amino acid oxidase-coupled reaction adapted for microassay in wells of disposotrays is described. Susceptible amino acids in the presence of oxidase produce hydrogen peroxide, which combines with dianisidine to give a colored product. Immediately following column chromatography effluent fractions can be scanned simultaneously for peptidase activity toward several substrates. Color production enables direct visualization of relative rates of peptide cleavage as hydrolysis proceeds. This microassay enables one to simultaneously localize peptidases in effluent fractions following chromatography, gain information concerning substrate specificity of each peptidase eluted, and estimate the relative rates of hydrolysis of a given peptide by several enzymes.     

Physical linkage of mouse Tcrg-V genes. II. Regulatory features of the Vg4-Vg3 intergenic region

The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number L20 100.     

Learning protein multi-view features in complex space

Protein attribute prediction from primary sequences is an important task and how to extract discriminative features is one of the most crucial aspects. Because single-view feature cannot reflect all the information of a protein, fusing multi-view features is considered as a promising route to improve prediction accuracy. In this paper, we propose a novel framework for protein multi-view feature fusion: first, features from different views are parallely combined to form complex feature vectors; Then, we extend the classic principal component analysis to the generalized principle component analysis for further feature extraction from the parallely combined complex features, which lie in a complex space. Finally, the extracted features are used for prediction. Experimental results on different benchmark datasets and machine learning algorithms demonstrate that parallel strategy outperforms the traditional serial approach and is particularly helpful for extracting the core information buried among multi-view feature sets. A web server for protein structural class prediction based on the proposed method (COMSPA) is freely available for academic use at: http://www.csbio.sjtu.edu.cn/bioinf/COMSPA/.     

An ensemble approach to accurately detect somatic mutations using SomaticSeq

SomaticSeq is an accurate somatic mutation detection pipeline implementing a stochastic boosting algorithm to produce highly accurate somatic mutation calls for both single nucleotide variants and small insertions and deletions. The workflow currently incorporates five state-of-the-art somatic mutation callers, and extracts over 70 individual genomic and sequencing features for each candidate site. A training set is provided to an adaptively boosted decision tree learner to create a classifier for predicting mutation statuses. We validate our results with both synthetic and real data. We report that SomaticSeq is able to achieve better overall accuracy than any individual tool incorporated.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0758-2) contains supplementary material, which is available to authorized users.