Computational approaches to understanding the protein structure

This thesis is composed of two different parts, aiming to predict and understand the protein structure from their contact maps. In the first part, residue contacts of a protein are predicted using neural networks in order to obtain structural constraints for the three-dimensional structure. Physical and chemical properties of residues and their primary sequence neighbors are used for the prediction. Our predictor can predict 11% of the contacting residuees with a false positive ratio of 2% and it performs 7 times better than a random predictor. In the second part, a new method is developed to model a protein as a network of its interacting residues. Small-world network concept is utilized to interpret the parameters of residue networks. It is concluded that proteins are neither regular nor randomly packed but between these two extremes. Such a structure gives the proteins the ability for fast information relay between their residues. They can undergo necessary conformational changes for their functions on very short time scales. Also, residuee networks are shown to obey a truncated power-law degree distribution instead of being scale-free. This shows that proteins have fewer structurally weak points, whose failure would be total damage for the system. This finding conforms to evolutionary plasticity of proteins: Having a low number of weak points makes the mild DNA mutations to be tranlated into the protein structure as highly tolerable

Small-world communication of residues and significance for protein dynamics

It is not merely the position of residues that are of utmost importance in protein function and stability, but the interactions between them. We illustrate, by using a network construction on a set of 595 non-homologous proteins, that regular packing is preserved in short-range interactions, but short average path lengths are achieved through some long-range contacts. Thus, lying between the two extremes of regularity and randomness, residues in folded proteins are distributed according to a "small-world" topology. Using this topology, we show that the core residues have the same local packing arrangements irrespective of protein size. Furthermore, we find that the average shortest path lengths are highly correlated with residue fluctuations, providing a link between the spatial arrangement of the residues and protein dynamics.Comment: 18 pages, 6 figures, submitted to Biophys.

Utjecaj korištenja probiotika i prebiotika na aromatske spojeve i teksturalna i senzorska svojstva simbiotskog kozjeg sira

The aim of this study was to evaluate the effects of probiotics as an adjunct culture, and the use of inulin and oligofructose as a prebiotic product, on symbiotic goat cheeses during their ripening period. The control group had the lowest value in terms of aromatic compounds, and the probiotics used in the production of cheese increased the aromatic substances. The control group was found to have the highest hardness values and that the use of prebiotics and probiotic cultures in cheese production significantly changed the textural profile depending on the probiotic and prebiotic type. The most favoured cheeses were found to contain E. faecium and oligofructose.U ovom radu istražen je utjecaj probiotika, te inulina i oligofruktoze, na simbiotski kozji sir tijekom zrenja. U kontrolnoj grupi su utvrđene najniže koncentracije aromatskih spojeva, dok je dodatak probiotika u proizvodnji sira povećao koncentraciju aromatskih spojeva. Također, u sirevima iz kontrolne grupe su utvrđene najveće vrijednosti čvrstoće. Dodatak probiotika i prebiotika je signifikantno utjecao na teksturalne karakteristike sira. Sirevi koji su ocjenjeni kao najbolji, proizvedeni su uz dodatak E. facium i oligofruktoze

Investigation of the effect of book reading activity on attention level and reaction time in student athletes

The aim of this study is to investigate the effect of regular book reading activity on attention level and reaction time in student athletes. The study group consists of 33 student athletes, 17 individuals in control group and 16 individuals in experiment group, doing individual or team sports. Experiment group read books for a period of 40 minutes, three times a week. In addition to personal information form, “Visual Attention Test” is applied to volunteers. The data of the research were evaluated in the SPSS program. Differences were observed in reaction time of students who regularly read books and not (p<0.05). While no difference was observed in accuracy ratio of student athletes who do not read books, differences were found in student athletes who read (p<0.05). While no differences were observed on accuracy ratio of student athletes doing individual sports who do not read books regularly, differences were determined on accuracy ratio of student athletes doing team sports. There were differences on accuracy ratio of student athletes doing individual sports or team sports and who read books regularly. In conclusion, it is determined that students doing individual sports or team sports who read books regularly have better attention levels compared to those who do not read books

Exploration of signals of positive selection derived from genotype-based human genome scans using re-sequencing data.

We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions (chr4:158Mb and chr10:22Mb) lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene SPAG6 in the other

Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus

Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D), focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip) and absolute methylation values were estimated using a Bayesian algorithm (BATMAN). Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10−4, permutation p = 1.0×10−3). Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10−7). Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA) SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases

A Histone Map of Human Chromosome 20q13.12

We present a systematic search for regulatory elements in a 3.5 Mb region on human chromosome 20q13.12, a region associated with a number of medical conditions such as type II diabetes and obesity.We profiled six histone modifications alongside RNA polymerase II (PolII) and CTCF in two cell lines, HeLa S3 and NTERA-2 clone D1 (NT2/D1), by chromatin immunoprecipitation using an in-house spotted DNA array, constructed with 1.8 kb overlapping plasmid clones. In both cells, more than 90% of transcription start sites (TSSs) of expressed genes showed enrichments with PolII, di-methylated lysine 4 of histone H3 (H3K4me2), tri-methylated lysine 4 of histone H3 (H3K4me3) or acetylated H3 (H3Ac), whereas mono-methylated lysine 4 of histone H3 (H3K4me1) signals did not correlate with expression. No TSSs were enriched with tri-methylated lysine 27 of histone H3 (H3K27me3) in HeLa S3, while eight TSSs (4 expressed) showed enrichments in NT2/D1. We have also located several CTCF binding sites that are potential insulator elements.In summary, we annotated a number of putative regulatory elements in 20q13.12 and went on to verify experimentally a subset of them using dual luciferase reporter assays. Correlating this data to sequence variation can aid identification of disease causing variants