Quantitative analysis of ChIP-seq signals and transcriptomes

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) is commonly used to analyze the in vivo interactions between proteins and DNA across the genome. Analysis of ChIP-seq data has largely focused on detection of presence of peaks that represent DNA regions enriched by chromatin immunoprecipitation, i.e., the DNA loci bound by the immunoprecipitated proteins. To properly interpret ChIP-seq data, capturing its quantitative features is imperative. In this dissertation, we develop a statistically robust pipeline, named as ChIP-seq Signal Quantifier (CSSQ), that provides normalized ChIP-seq data, enabling detection and quantification of differential binding (DBs) across the genome, allowing calculable comparisons among multiple ChIP-seq datasets on predefined regions. Using both experimental datasets and computational simulations, we demonstrate the superior performance of CSSQ against existing tools as evidenced by its high sensitivity and specificity, and low false discovery rate. CSSQ is applicable to ChIP-seq datasets with varied signal to noise ratio, significantly improving the accuracy of comparison of ChIP-seq datasets from different experiments, serving as a powerful pipeline suited to garner quantitative information from ChIP-seq datasets for deciphering epigenomes. RNA-seq has become the leading choice for transcriptome analysis. Using RNA-seq and bioinformatics analysis, we characterize gene expression profiles and key cellular processes during stem cell differentiation and cell responses upon nanoparticle exposure. Collectively, these studies show that transcriptome analysis is a powerful tool for characterization and understanding cellular mechanisms.Ph.D

Detecting Networks Employing Algorithmically Generated Domain Names

Recent Botnets such as Conficker, Kraken and Torpig have used DNS based "domain fluxing" for command-and-control, where each Bot queries for existence of a series of domain names and the owner has to register only one such domain name. In this report, we develop a methodology to detect such "domain fluxes" in DNS traffic by looking for patterns inherent to domain names that are generated algorithmically, in contrast to those generated by humans. In particular, we look at distribution of alphanumeric characters as well as bigrams in all domains that are mapped to the same set of IP-addresses. We present and compare the performance of several distance metrics, including KL-distance and Edit distance. We train by using a good data set of domains obtained via a crawl of domains mapped to all IPv4 address space and modeling bad data sets based on behaviors seen so far and expected. We also apply our methodology to packet traces collected at two Tier-1 ISPs and show we can automatically detect domain fluxing as used by Conficker botnet with minimal false positives. We are also able to detect new botnets and other malicious networks using our method

Characterization Studies on Graphene-Aluminium Nano Composites for Aerospace Launch Vehicle External Fuel Tank Structural Application

From the aspect of exploring the alternative lightweight composite material for the aerospace launch vehicle external fuel tank structural components, the current research work studies three different grades of Aluminium alloy reinforced with varying graphene weight percentages that are processed through powder metallurgy (P/M) route. The prepared green compacts composite ingots are subjected to microwave processing (Sintering), hot extruded, and solution treated (T6). The developed Nano-graphene reinforced composite is studied further for the strength–microstructural integrity. The nature of the graphene reinforcement and its chemical existence within the composite is further studied, and it is found that hot extruded solution treated (HEST) composite exhibited low levels of carbide (Al4C3) formations, as composites processed by microwaves. Further, the samples of different grades reinforced with varying graphene percentages are subjected to mechanical characterisation tests such as the tensile test and hardness. It is found that 2 wt% graphene reinforced composites exhibited enhanced yield strength and ultimate tensile strength. Microstructural studies and fracture morphology are studied, and it is proven that composite processed via the microwave method has exhibited good ductile behaviour and promising failure mechanisms at higher load levels

An uncommon variant of rare type of muscular dystrophy

The muscular dystrophies are a group of hereditary degenerative diseases characterised by progressive myopathy. Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetically heterogenous type of muscular dystrophy characterized by early contractures (especially in the neck, elbows and ankles), slowly progressing muscle weakness more prominent in humeroperoneal region, onset in early childhood and cardiac problems. Emery-Dreifuss muscular dystrophy is commonly inherited in an X linked recessive pattern and rarely autosomal dominant inheritance or autosomal recessive fashion. Here we report a case of autosomal recessive type of Emery-Dreifuss muscular dystrophy from our hospital

A Comparative Study of Mean Platelet Volume in Diabetic Population With and Without Vascular Complication

Diabetes mellitus leads to long-term complications involving multiple organs and systems of the human body. Among the list of complications, a relatively vascular complication increases the morbidity of the condition. Patients with diabetes mellitus are influenced by various factors like hyperglycaemic state, insulin resistance, oxidative stress, and metabolic condition like obesity, and all the mentioned conditions also present with platelet hyperactivity.  Mean platelet volume (MPV) can be used as one of the laboratory parameters to know the function and activation of the platelets, which reflects the vascular profile of the patient. So, the present study compares the values of mean platelet volume among the diabetic groups to determine the relation between the vascular complication and the mean platelet volume. This study was conducted with 90 participants, who were divided into three groups. Group A  is non-diabetics, group B is type 2 Diabetics, and Group C is type 2 Diabetics with vascular complications and MPV.  On analyzing the statistical mean value of mean platelet volume, group B's (type 2 diabetics) value was higher than group A's (non-diabetics) and statistically significant with a p – value of 0.001. Similarly, the mean value of group C (type 2 diabetes with complications) was higher than group B (type 2 diabetics) and statistically significant with a p – value of 0.049 in the diabetics with and without vascular complications. On comparing the MPV of different study groups, the MPV is higher in the diabetic group with complicatiosn compared with the diabetics without complications

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London