Ensemble learning based assessment of the role of transcription factors in gene expression.

Cancer cells are formed when the associated, active genes fail to function the way they are meant to function. Multiple genes collectively control cell growth by activating a proper set of genes. Regulation of gene expression is controlled through the combined effort of multiple regulatory elements. Transcription of each gene is affected differently according to the combinatorial patterns of regulatory elements bound in the nearby regions. Identifying and analysing such patterns will give a better insight into the cell function. The main focus of this study is on developing a computational model to predict the functional role of transcriptional factors residing between divergent gene pairs. Acute Myeloid Leukaemia (AML) gene expression data from GEO and the two TFs EP300 and CTCF binding data calibrated in k562 cell line from ENCODE consortium are taken as a case study.

FPTMS: Frequency-based approach to identify the peptide from the low-energy collision-induced dissociation tandem mass spectra.

The database search method is a widely accepted method to assign a peptide to the tandem mass spectra. In this study, a new flexible method- FPTMS is introduced to interpret the tandem mass spectra with the known peptide sequences in a protein database. Here the frequency of occurrence of fragment ion peaks extracted from the extensive spectral library is used to predict the theoretical tandem mass spectra of the peptides. The dot product scoring and windowed-xcorr scoring methods were implemented to score the experimental spectrum against the theoretical peptide spectra. Windowed-xcorr is introduced to tackle the mass errors and the cleavage position of the fragmentation process. The new method with windowed-xcorr shows an improved identification rate compared to the existing search engines Crux-Tide and X!Tandem at 1% False Discovery Rate (FDR) for the dataset considered in this study. SIGNIFICANCE: Identifying or sequencing of the peptide from tandem mass spectra is an important application in mass spectrometry-based proteomics. Collision-induced dissociation (CID) fragmentation spectra have been widely used to develop a peptide identification algorithm using database search strategy. CID fragmentation behavior is a complex process and found to have dependency on the sequences of peptide, charge state, and residue content. The inclusion of more features of peptide fragmentation behavior and adaptable scoring algorithm improves the efficiency of the peptide identification algorithm.

A Frequency-Based Approach to Predict the Low-Energy Collision-Induced Dissociation Fragmentation Spectra.

Peptide identification algorithms rely on the comparison between the experimental tandem mass spectrometry spectrum and the theoretical spectrum to identify a peptide from the tandem mass spectra. Hence, it is important to understand the fragmentation process and predict the tandem mass spectra for high-throughput proteomics research. In this study, a novel method was developed to predict the theoretical ion trap collision-induced dissociation (CID) tandem mass spectra of the singly, doubly, and triply charged tryptic peptides. The fragmentation statistics of the ion trap CID spectra were used to predict the theoretical tandem mass spectra of the peptide sequence. The study estimated the relative cleavage frequency for each pair of adjacent amino acids along the peptide length. The study showed that the cleavage frequency can be directly used to predict the tandem mass spectra. The predicted spectra show a high correlation with the experimental spectra used in this study; 99.73% of the high-quality reference spectra have correlation scores greater than 0.8. The new method predicts the theoretical spectrum and correlates significantly better with the experimental spectrum as compared to the existing spectrum prediction tools OpenMS_Simulator, MS2PIP, and MS2PBPI, where only 80, 85.76, and 85.80% of the spectral count, respectively, has a correlation score greater than 0.8.

Exon Mapping in Long Noncoding RNAs Using Digital Filters.

Long noncoding RNAs (lncRNAs) which were initially dismissed as "transcriptional noise" have become a vital area of study after their roles in biological regulation were discovered. Long noncoding RNAs have been implicated in various developmental processes and diseases. Here, we perform exon mapping of human lncRNA sequences (taken from National Center for Biotechnology Information GenBank) using digital filters. Antinotch digital filters are used to map out the exons of the lncRNA sequences analyzed. The period 3 property which is an established indicator for locating exons in genes is used here. Discrete wavelet transform filter bank is used to fine-tune the exon plots by selectively removing the spectral noise. The exon locations conform to the ranges specified in GenBank. In addition to exon prediction, G-C concentrations of lncRNA sequences are found, and the sequences are searched for START and STOP codons as these are indicators of coding potential.

Novel Approach to Analyzing MFE of Noncoding RNA Sequences.

Genomic studies have become noncoding RNA (ncRNA) centric after the study of different genomes provided enormous information on ncRNA over the past decades. The function of ncRNA is decided by its secondary structure, and across organisms, the secondary structure is more conserved than the sequence itself. In this study, the optimal secondary structure or the minimum free energy (MFE) structure of ncRNA was found based on the thermodynamic nearest neighbor model. MFE of over 2600 ncRNA sequences was analyzed in view of its signal properties. Mathematical models linking MFE to the signal properties were found for each of the four classes of ncRNA analyzed. MFE values computed with the proposed models were in concordance with those obtained with the standard web servers. A total of 95% of the sequences analyzed had deviation of MFE values within ±15% relative to those obtained from standard web servers.

Experiments with a novel content-based image retrieval software: can we eliminate classification systems in adolescent idiopathic scoliosis?

Study Design Preliminary evaluation of new tool. Objective To ascertain whether the newly developed content-based image retrieval (CBIR) software can be used successfully to retrieve images of similar cases of adolescent idiopathic scoliosis (AIS) from a database to help plan treatment without adhering to a classification scheme. Methods Sixty-two operated cases of AIS were entered into the newly developed CBIR database. Five new cases of different curve patterns were used as query images. The images were fed into the CBIR database that retrieved similar images from the existing cases. These were analyzed by a senior surgeon for conformity to the query image. Results Within the limits of variability set for the query system, all the resultant images conformed to the query image. One case had no similar match in the series. The other four retrieved several images that were matching with the query. No matching case was left out in the series. The postoperative images were then analyzed to check for surgical strategies. Broad guidelines for treatment could be derived from the results. More precise query settings, inclusion of bending films, and a larger database will enhance accurate retrieval and better decision making. Conclusion The CBIR system is an effective tool for accurate documentation and retrieval of scoliosis images. Broad guidelines for surgical strategies can be made from the postoperative images of the existing cases without adhering to any classification scheme.

Molecular phylogeny analysis using correlation distance and spectral distance.

A wide range of methods with or without sequence alignment have been used to study molecular phylogeny for information on the evolution of species. Two approaches to construct the phylogenetic tree using (a) direct correlation of protein sequences and (b) difference between the Discrete Fourier Transform coefficients are described. The proposed methods use a transformation where each amino acid is represented by its Electron-Ion Interaction Potential (EIIP) value. Phylogenetic tree of two mammalian orders, primates and cetacea, is generated based on Fitch-Margoliash, Neighbour-Joining and UPGMA methods and compared. The phylogenetic tree of evolutionary relationships thus obtained can be used for comparison of species and gene sequences. The information thus gathered provide meaningful insights into the pattern and process of evolution which will help researchers in developing new breeds of animals and plants.

Discrete wavelet transform de-noising in eukaryotic gene splicing.

BACKGROUND: This paper compares the most common digital signal processing methods of exon prediction in eukaryotes, and also proposes a technique for noise suppression in exon prediction. The specimen used here which has relevance in medical research, has been taken from the public genomic database - GenBank. METHODS: Here exon prediction has been done using the digital signal processing methods viz. binary method, EIIP (electron-ion interaction psuedopotential) method and filter methods. Under filter method two filter designs, and two approaches using these two designs have been tried. The discrete wavelet transform has been used for de-noising of the exon plots. RESULTS: Results of exon prediction based on the methods mentioned above, which give values closest to the ones found in the NCBI database are given here. The exon plot de-noised using discrete wavelet transform is also given. CONCLUSION: Alterations to the proven methods as done by the authors, improves performance of exon prediction algorithms. Also it has been proven that the discrete wavelet transform is an effective tool for de-noising which can be used with exon prediction algorithms.

A new fast fractal modeling approach for the detection of microcalcifications in mammograms.

In this paper, a novel fast method for modeling mammograms by deterministic fractal coding approach to detect the presence of microcalcifications, which are early signs of breast cancer, is presented. The modeled mammogram obtained using fractal encoding method is visually similar to the original image containing microcalcifications, and therefore, when it is taken out from the original mammogram, the presence of microcalcifications can be enhanced. The limitation of fractal image modeling is the tremendous time required for encoding. In the present work, instead of searching for a matching domain in the entire domain pool of the image, three methods based on mean and variance, dynamic range of the image blocks, and mass center features are used. This reduced the encoding time by a factor of 3, 89, and 13, respectively, in the three methods with respect to the conventional fractal image coding method with quad tree partitioning. The mammograms obtained from The Mammographic Image Analysis Society database (ground truth available) gave a total detection score of 87.6%, 87.6%, 90.5%, and 87.6%, for the conventional and the proposed three methods, respectively.

Content-based image retrieval of spine radiographs with scoliosis.

STUDY DESIGN: Description of a novel application. OBJECTIVE: Proposal of a new system for content-based image retrieval (CBIR) of scoliosis images for the retrieval of clinically similar images to a query image on the basis of automatically derived features. BACKGROUND: Variability exists in the selection of strategic vertebrae, measurement of Cobb angle, and assignment of a curve type in a classification scheme for scoliosis images. Besides, many classification schemes are in use today, creating ambiguity in selecting a particular classification scheme. METHODS: A rule-based algorithm for strategic vertebrae selection and Cobb angle measurement was developed. A set of automatically derived features necessary for indexing the scoliosis image for CBIR was formulated. A hybrid CBIR system is proposed in which scoliosis features and treatment procedure along with preoperative and postoperative images are integrated. The system was evaluated using 30 curves on standing anteroposterior scoliosis images. The measurement was carried out by 3 independent observers who measured twice at an interval of 7 days. RESULTS: The average difference in Cobb angle was 2.0 degrees with a standard deviation of 3.0 degrees. High values for the correlation coefficient were obtained for both interobserver and intraobserver assessment, proving the repeatability of the system. The CBIR system was validated by query-by-example test method and the system could retrieve correct sets of clinically matching images in the increasing order of distance. CONCLUSIONS: The newly developed system is an accurate and reliable system for search and retrieval of scoliosis images. On querying with a new image, the therapeutic strategy for surgical planning can be assigned on the basis of the outcome assessment of the most similar images retrieved, thereby reducing the importance of any classification scheme.

Automatic estimation of orientation and position of spine in digitized X-rays using mathematical morphology.

In this paper, we propose a method for automatic determination of position and orientation of spine in digitized spine X-rays using mathematical morphology. As the X-ray images are usually highly smeared, vertebrae segmentation is a complex process. The image is first coarsely segmented to obtain the location and orientation information of the spine. The state-of-the-art technique is based on the deformation model of a template, and as the vertebrae shape usually shows variation from case to case, accurate representation using a template is a difficult process. The proposed method makes use of the vertebrae morphometry and gray-scale profile of the spine. The top-hat transformation-based method is proposed to enhance the ridge points in the posterior boundary of the spine. For cases containing external objects such as ornaments, H-Maxima transform is used for segmentation and removal of these objects. The Radon transform is then used to estimate the location and orientation of the line joining the ridge point clusters appearing on the boundary of the vertebra body. The method was validated for 100 cervical spine X-ray images, and in all cases, the error in orientation was within the accepted tolerable limit of 15 degrees. The average error was found to be 4.6 degrees. A point on the posterior boundary was located with an accuracy of +/-5.2 mm. The accurate information about location and orientation of the spine is necessary for fine-grained segmentation of the vertebrae using techniques such as active shape modeling. Accurate vertebrae segmentation is needed in successful feature extraction for applications such as content-based image retrieval of biomedical images.

Multiplexed wavelet transform technique for detection of microcalcification in digitized mammograms.

Wavelet transform (WT) is a potential tool for the detection of microcalcifications, an early sign of breast cancer. This article describes the implementation and evaluates the performance of two novel WT-based schemes for the automatic detection of clustered microcalcifications in digitized mammograms. Employing a one-dimensional WT technique that utilizes the pseudo-periodicity property of image sequences, the proposed algorithms achieve high detection efficiency and low processing memory requirements. The detection is achieved from the parent-child relationship between the zero-crossings [Marr-Hildreth (M-H) detector] /local extrema (Canny detector) of the WT coefficients at different levels of decomposition. The detected pixels are weighted before the inverse transform is computed, and they are segmented by simple global gray level thresholding. Both detectors produce 95% detection sensitivity, even though there are more false positives for the M-H detector. The M-H detector preserves the shape information and provides better detection sensitivity for mammograms containing widely distributed calcifications.