Mean Squared Residue Based Biclustering Algorithms for the Analysis of Gene Expression Data

Computational Biology is the research are that contributes to the analysis of biological data through the development of algorithms which will address significant research problems.The data from molecular biology includes DNA,RNA ,Protein and Gene expression data.Gene Expression Data provides the expression level of genes under different conditions.Gene expression is the process of transcribing the DNA sequence of a gene into mRNA sequences which in turn are later translated into proteins.The number of copies of mRNA produced is called the expression level of a gene.Gene expression data is organized in the form of a matrix. Rows in the matrix represent genes and columns in the matrix represent experimental conditions.Experimental conditions can be different tissue types or time points.Entries in the gene expression matrix are real values.Through the analysis of gene expression data it is possible to determine the behavioral patterns of genes such as similarity of their behavior,nature of their interaction,their respective contribution to the same pathways and so on. Similar expression patterns are exhibited by the genes participating in the same biological process.These patterns have immense relevance and application in bioinformatics and clinical research.Theses patterns are used in the medical domain for aid in more accurate diagnosis,prognosis,treatment planning.drug discovery and protein network analysis.To identify various patterns from gene expression data,data mining techniques are essential.Clustering is an important data mining technique for the analysis of gene expression data.To overcome the problems associated with clustering,biclustering is introduced.Biclustering refers to simultaneous clustering of both rows and columns of a data matrix. Clustering is a global whereas biclustering is a local model.Discovering local expression patterns is essential for identfying many genetic pathways that are not apparent otherwise.It is therefore necessary to move beyond the clustering paradigm towards developing approaches which are capable of discovering local patterns in gene expression data.A biclusters is a submatrix of the gene expression data matrix.The rows and columns in the submatrix need not be contiguous as in the gene expression data matrix.Biclusters are not disjoint.Computation of biclusters is costly because one will have to consider all the combinations of columans and rows in order to find out all the biclusters.The search space for the biclustering problem is 2 m+n where m and n are the number of genes and conditions respectively.Usually m+n is more than 3000.The biclustering problem is NP-hard.Biclustering is a powerful analytical tool for the biologist.The research reported in this thesis addresses the problem of biclustering.Ten algorithms are developed for the identification of coherent biclusters from gene expression data.All these algorithms are making use of a measure called mean squared residue to search for biclusters.The objective here is to identify the biclusters of maximum size with the mean squared residue lower than a given threshold. All these algorithms begin the search from tightly coregulated submatrices called the seeds.These seeds are generated by K-Means clustering algorithm.The algorithms developed can be classified as constraint based,greedy and metaheuristic.Constarint based algorithms uses one or more of the various constaints namely the MSR threshold and the MSR difference threshold.The greedy approach makes a locally optimal choice at each stage with the objective of finding the global optimum.In metaheuristic approaches particle Swarm Optimization(PSO) and variants of Greedy Randomized Adaptive Search Procedure(GRASP) are used for the identification of biclusters.These algorithms are implemented on the Yeast and Lymphoma datasets.Biologically relevant and statistically significant biclusters are identified by all these algorithms which are validated by Gene Ontology database.All these algorithms are compared with some other biclustering algorithms.Algorithms developed in this work overcome some of the problems associated with the already existing algorithms.With the help of some of the algorithms which are developed in this work biclusters with very high row variance,which is higher than the row variance of any other algorithm using mean squared residue, are identified from both Yeast and Lymphoma data sets.Such biclusters which make significant change in the expression level are highly relevant biologically.

A novel Sigma–Delta based parallel analogue-to-residue converter

Animportant step in the residue number system(RNS) based signal processing is the conversion of signal into residue domain. Many implementations of this conversion have been proposed for various goals, and one of the implementations is by a direct conversion from an analogue input. A novel approach for analogue-to-residue conversion is proposed in this research using the most popular Sigma–Delta analogue-to-digital converter (SD-ADC). In this approach, the front end is the same as in traditional SD-ADC that uses Sigma–Delta (SD) modulator with appropriate dynamic range, but the filtering is doneby a filter implemented usingRNSarithmetic. Hence, the natural output of the filter is an RNS representation of the input signal. The resolution, conversion speed, hardware complexity and cost of implementation of the proposed SD based analogue-to-residue converter are compared with the existing analogue-to-residue converters based on Nyquist rate ADCs

Mechanisms of residue mulch-induced cereal growth increases in West Africa

The use of crop residues (CR) has been widely reported as a means of increasing crop yields across West Africa. However, little has been done to compare the magnitude and mechanisms of CR effects systematically in the different agro-ecological zones of the region. To this end, a series of field trials with millet (Pennisetum glaucum L.), sorghum [Sorghum bicolor (L.) Moench], and maize (Zea mays L.) was conducted over a 4-yr period in the Sahelian, Sudanian, and Guinean zones of West Africa. Soils ranged in pH from 4.1 to 5.4 along a rainfall gradient from 510 to 1300 mm. Treatments in the factorial experiments were three CR rates (0,500, and 2000 kg ha^-1)and several levels of phosphorus and nitrogen. The results showed CR-induced total dry matter (TDM) increases in cereals up to 73% for the Sahel compared with a maximum of 16% in the wetter Sudanian and Guinean zones. Residue effects on weakly buffered Sahelian soils were due to improved P availability and to a protection of seedlings against wind erosion. Additional effects of CR mulching on topsoil properties in the Sahel were a decrease in peak temperatures by 4°C and increased water availability. These mulch effects on soil chemical and physical properties strongly decreased from North to South. Likely explanations for this decrease are the decline of dust deposition and wind erosion hazards, the higher soil clay content, lower air temperature, and a faster decomposition rate of mulch material with increasing rainfall from the Sahel to the Sudanian and Guinean zones.

Destructive and non-destructive measurements of residual crop residue and phosphorus effects on growth and composition of herbaceous fallow species in the Sahel

Little is known about the residual effects of crop residue (CR) and phosphorus (P) application on the fallow vegetation following repeated cultivation of pearl millet [Pennisetum glaucum (L.) R. Br.] in the Sahel. The objective of this study, therefore, was (i) to measure residual effects of CR, mulched at annual rates of 0, 500, 1000 and 2000 kg CR ha^-1, broadcast P at 0 and 13 kg P ha^-1 and P placement at 0, 1, 3, 5 and 7 kg P ha^-1 on the herbaceous dry matter (HDM) 2 years after the end of the experiment and (ii) to test a remote sensing method for the quantitative estimation of HDM. Compared with unmulched plots, a doubling of HDM was measured in plots that had received at least 500 kg CR ha^-1. Previous broadcast P application led to HDM increases of 14% compared with unfertilised control plots, whereas no residual effects of P placement were detected. Crop residue and P treatments caused significant shifts in flora composition. Digital analysis of colour photographs taken of the fallow vegetation and the bare soil revealed that the number of normalised green band pixels averaged per plot was highly correlated with HDM (r=0.86) and that red band pixels were related to differences in soil surface crusting. Given the traditional use of fallow vegetation as fodder, the results strongly suggest that for the integrated farming systems of the West African Sahel, residual effects of soil amendments on the fallow vegetation should be included in any comprehensive analysis of treatment effects on the agro-pastoral system.

Decomposition and phosphorus release from organic residues as affected by residue quality and added inorganic phosphorus

The combined use of organic residue and inorganic fertiliser-phosphorus (P) is appropriate in meeting both the short and long-term P requirement of crops. To assess the influence of added inorganic fertiliser-P on the processes of decomposition and P release from the residue and the relationships with quality, prunings of Gliricidia sepium, Leucaena leucocephela, Senna siamea, Acacia mangium and Paraserienthus falcataria were incubated without and with added inorganic fertiliser-P for 56 days. Soil was added only as inoculum. Decomposition rate and amounts of acid extractable-P (P release) were in the same order: G. sepium > S. siamea > L. leucocepheta > P falcataria > A. mangium. Unlike the other residues, A. mangium released no P despite the loss of half its mass during the 8 weeks of incubation. The residue P content correlated with P release. However, decomposition rate did not correlate with residue P content but with the lignin, polyphenol and cellulose content, and ratios to P. These ratios were negatively correlated with P release suggesting that lignin and polyphenol contents influence P release more when the residue-P content is low. Results suggest that rate of decomposition influences the release of P. The critical residue P content for P release was estimated to be 0.12% < P < 0.19%. Added P had no effect on decomposition and P release from the residues.

Utilisation by upland rice of plant residue- and fertiliser-phosphorus in two tropical acid soils

A dual isotopic technique was used to assess the effects of soil type, and residues of Gliricidia sepium, without and with added fertiliser-P on the utilisation of P. Upland rice (Oryza sativa) was grown for 70 days in two tropical acid soils of different P sorbing capacity and P status. Uniformly P-32-labelled soils were treated with inorganic fertiliser-P tagged with P-33, Gliricidia sepium residue applied at planting and 3 weeks earlier, and in a combination of fertiliser-P and Gliricidia applied at and 3 weeks before planting. There were significant responses of shoot and root weights, and total P uptake to Gliricidia- and/or fertiliser-P addition in the Ultisol (low P status) but not the Oxisol (high P status), suggesting that P in the latter soil was not yield limiting, despite the high standard P requirement. Similarly, incorporation of Gliricidia three weeks before planting further increased shoot weight only in the Ultisol. There were generally higher proportions, quantities and percent utilisations of the Gliricidia- P and fertiliser-P in the Ultisol than in the Oxisol. Gliricidia significantly increased the utilisation of fertiliser-P only in the Ultisol. However, early application of Gliricidia increased Gliricidia- P but not fertiliser-P utilisation in the Ultisol. Added fertiliser-P did not influence Gliricidia- P utilisation.

The use of FT-IR as a screening technique for organic residue analysis of archaeological samples

A range of archaeological samples have been examined using FT-IR spectroscopy. These include suspected coprolite samples from the Neolithic site of Catalhoyuk in Turkey, pottery samples from the Roman site of Silchester, UK and the Bronze Age site of Gatas, Spain and unidentified black residues on pottery sherds from the Roman sites of Springhead and Cambourne, UK. For coprolite samples the aim of FT-IR analysis is identification. Identification of coprolites in the field is based on their distinct orange colour; however, such visual identifications can often be misleading due to their similarity with deposits such as ochre and clay. For pottery the aim is to screen those samples that might contain high levels of organic residues which would be suitable for GC-MS analysis. The experiments have shown coprolites to have distinctive spectra, containing strong peaks from calcite, phosphate and quartz; the presence of phosphorus may be confirmed by SEM-EDX analysis. Pottery containing organic residues of plant and animal origin has also been shown to generally display strong phosphate peaks. FT-IR has distinguished between organic resin and non-organic compositions for the black residues, with differences also being seen between organic samples that have the same physical appearance. Further analysis by CC-MS has confirmed the identification of the coprolites through the presence of coprostanol and bile acids, and shows that the majority of organic pottery residues are either fatty acids or mono- or di-acylglycerols from foodstuffs, or triterpenoid resin compounds exposed to high temperatures. One suspected resin sample was shown to contain no organic residues. and it is seen that resin samples with similar physical appearances have different chemical compositions. FT-IR is proposed as a quick and cheap method of screening archaeological samples before subjecting them to the more expensive and time-consuming method of GC-MS. This will eliminate inorganic samples such as clays and ochre from CC-MS analysis, and will screen those samples which are most likely to have a high concentration of preserved organic residues. (C) 2008 Elsevier B.V. All rights reserved.

Consumer attitudes towards and willingness to pay for pesticide residue limit compliant 'safe' vegetables in Northeast Thailand

Pesticide residue in vegetables is a major food safety issue in Thailand. A range of vegetable products (organic/pesticide-free/ hydroponic) has emerged in Thai markets that guarantee compliance with maximum residue limits. The Government of Thailand is eager to extend the benefits of this suite of alternative vegetables to the entire population, particularly the semi-urban/rural segments that are often bypassed by such speciality products. However, little information is available to guide such an effort, particularly with regard to up-country consumer attitudes, shopping and consumption habits and willingness to pay premiums for such produce. This research aims to fill this gap in knowledge. It reports the results of a survey of vegetable consumption and shopping habits and attitudes of 608 consumers in northeast Thailand. Willingness to pay premiums for pesticide residue limit compliant vegetables is also assessed by using a contingent valuation method, and determinants of willingness to pay are examined using an ordered probit empirical model. Results indicate that, given adequate awareness of relative risks, even up-country consumers are willing to pay market premium levels for these products, and that inadequate availability, rather than lack of demand is the constraining factor. Willingness to pay is found to increase with income, age and supermarket sourcing of vegetables. We also discuss the challenge of improving availability at mainstream outlets.

The effect of wheat straw residue on the emergence and early growth of sugar beet (Beta vulgaris) and oilseed rape (Brassica napus)

The management of straw residue can be a concern in non-inversion tillage systems where straw tends to be incorporated at shallow depths or left on the soil surface. This can lead to poor crop establishment because straw residue can impede or hinder crop emergence and growth. Small container-based experiments were undertaken using varying amounts of wheat straw residue either incorporated or placed oil the soil surface. The effects on (lays to seedling emergence, percentage emergence, seedling dry-weight and soil temperature using sugar beet and oilseed rape were investigated because these crops often follow wheat in a cropping sequence. The position of the straw residue was found to be the primary factor in reducing crop emergence and growth. Increasing the amount of straw residue (from 3.3 t ha(-1) to 6.7 t ha(-1)) did not show any consistent trends in reducing crop emergence or growth. However, in some instances, results indicated that an interaction between the position and the amount of straw residue Occurred particularly when the straw and seed was placed on the soil surface. Straw placed on the soil surface significantly reduced mean day-time soil temperature by approximately 2.5 degrees C compared to no residue. When the seed and straw was placed on the soil Surface a lack of seed-to-soil contact caused a reduction in emergence by approximately 30% because of the restriction in available moisture that limited the ability for seed imbibition. This trend was reversed when the seed was placed in the soil, but with straw residue still on the soil surface, because the surface straw was likely to reduce moisture evaporation and improved seed-to-soil contact that led to rapid emergence. In general, when straw was mixed in or placed on the soil surface along with the seed, sugar beet and oilseed rape emergence and early growth biomass was significantly restricted by approximately 50% compared to no residue. The consequences of placing seed with or near to straw residue have been shown to cause a restriction in crop establishment. In both oilseed tape and sugar beet, this could lead to a reduction in final crop densities, poor, uneven growth and potentially lower yields that could lower financial margins. Therefore, if farmers are planning to use non-inversion tillage methods for crop establishment, the management and removal of straw residue from near or above the seed is considered important for successful crop establishment. (C) 2008 Elsevier B.V. All rights reserved.

Supramolecular parallel beta-sheet and amyloid-like fibril forming peptides using delta-aminovaleric acid residue

Four terminally blocked tripeptides containing delta-aminovaleric acid residue self-assemble to form supramolecular beta-sheet structures as are revealed from their FT-IR data. Single crystal X-ray diffraction studies of two representative peptides also show that they form parallel beta-sheet structures. Self-aggregation of these beta-sheet forming peptides leads to the formation of fibrillar structures, as is evident from scanning electron microscopic (SEM) and transmission electron microscopic (TEM) images. These peptide fibrils bind to a physiological dye, Congo red and exhibit a typical green-gold birefringence under polarized light, showing close resemblance to neurodegenerative disease causing amyloid fibrils. (c) 2005 Elsevier Ltd. All rights reserved.

alpha-Aminoisobutyric acid modified protected analogues of beta-amyloid residue 17-20: a change from sheet to helix

The strong intermolecular interactions mediated by short hydrophobic sequences (e.g., 17-20, -L-Leu-L-Val-L-Phe-L-Phe-) in the middle of A beta are known to play a crucial role in the neuropathology of Alzheimer's disease. FTIR, TEM and Congo red binding studies indicated that a series of L-Ala substituted terminally protected peptides related to the sequence 17-20 of the beta-amyloid peptide, adopted D-sheet conformations. However, the Aib-modified analogues disrupt the D-sheet structure and switch over to a 310 helix with increasing number of Aib residues. X-ray crystallography shed some light on the change from sheet to helix at atomic resolution. (c) 2006 Elsevier Ltd. All rights reserved.

Supramolecular beta-sheet and nanofibril formation by self-assembling tripeptides containing an N-terminally located gamma-aminobutyric acid residue

Three terminally protected tripeptides Boc-gamma-Abu-Val-Leu-OMe 1, Boc-gamma-Abu-Leu-Phe-OMe 2 and Boc-gamma-Abu-Val-Tyr-OMe 3 (gamma-Abu = gamma-aminobutyric acid) each containing an N-terminally positioned gamma-aminobutyric acid residue have been synthesized, purified and studied. FT-IR studies of all these peptides revealed that these peptides form intermolecularly hydrogen bonded supramolecular beta-sheet structures. Peptides 1, 2 and 3 adopt extended backbone beta-strand molecular structures in crystals. Crystal packing of all these peptides demonstrates that these beta-strand structures self-assemble to form intermolecularly H-bonded parallel beta-sheet structures. Peptide 3 uses a side chain tyrosyl -OH group as an additional hydrogen bonding functionality in addition to the backbone CONH groups to pack in crystals. Transmission electron microscopic studies of all peptides indicate that they self-assemble to form nanofibrillar structures of an average diameter of 65 nm. These peptide fibrils exhibit amyloid-like behavior as they bind to a physiological dye Congo red and show a characteristic green-gold birefringence under polarizing microscope.

Nanozipper formation in the solid state from a self-assembling tripeptide with a single tryptophan residue

The self-assembly of a terminally protected tripeptide Boc-gamma-Abu(1)-Ala(2)-Trp(3)-OMe (gamma-Abu = gamma-aminobutyric acid) I results in the formation of a nanostructured supramolecular zipper through various non-covalent interactions in the crystal in which the indole side-chain of the Trp(3) residue plays a key role via N-H...pi interactions. (c) 2006 Published by Elsevier Ltd.

Stubs versus swabs? A comparison of gunshot residue collection techniques

The collection efficiency of two widely used gunshot residue (GSR) collection techniques—carbon-coated adhesive stubs and alcohol swabs—has been compared by counting the number of characteristic GSR particles collected from the firing hand of a shooter after firing one round. Samples were analyzed with both scanning electron microscopy and energy dispersive X-rays by an experienced GSR analyst, and the number of particles on each sample containing Pb, Ba, and Sb counted. The adhesive stubs showed a greater collection efficiency as all 24 samples gave positive results for GSR particles whereas the swabs gave only positive results for half of the 24 samples. Results showed a statistically significant collection efficiency for the stub collection method and likely reasons for this are considered.

FunFOLDQA: a quality assessment tool for protein-ligand binding site residue predictions

The estimation of prediction quality is important because without quality measures, it is difficult to determine the usefulness of a prediction. Currently, methods for ligand binding site residue predictions are assessed in the function prediction category of the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment, utilizing the Matthews Correlation Coefficient (MCC) and Binding-site Distance Test (BDT) metrics. However, the assessment of ligand binding site predictions using such metrics requires the availability of solved structures with bound ligands. Thus, we have developed a ligand binding site quality assessment tool, FunFOLDQA, which utilizes protein feature analysis to predict ligand binding site quality prior to the experimental solution of the protein structures and their ligand interactions. The FunFOLDQA feature scores were combined using: simple linear combinations, multiple linear regression and a neural network. The neural network produced significantly better results for correlations to both the MCC and BDT scores, according to Kendall’s τ, Spearman’s ρ and Pearson’s r correlation coefficients, when tested on both the CASP8 and CASP9 datasets. The neural network also produced the largest Area Under the Curve score (AUC) when Receiver Operator Characteristic (ROC) analysis was undertaken for the CASP8 dataset. Furthermore, the FunFOLDQA algorithm incorporating the neural network, is shown to add value to FunFOLD, when both methods are employed in combination. This results in a statistically significant improvement over all of the best server methods, the FunFOLD method (6.43%), and one of the top manual groups (FN293) tested on the CASP8 dataset. The FunFOLDQA method was also found to be competitive with the top server methods when tested on the CASP9 dataset. To the best of our knowledge, FunFOLDQA is the first attempt to develop a method that can be used to assess ligand binding site prediction quality, in the absence of experimental data.