Statistical methods for predicting genetic regulation

Transcriptional regulation of gene expression is essential for cellular differentiation and function, and defects in the process are associated with cancer. Transcription is regulated by the cis-acting regulatory regions and trans-acting regulatory elements. Transcription factors bind on enhancers and repressors and form complexes by interacting with each other to control the expression of the genes. Understanding the regulation of genes would help us to understand the biological system and can be helpful in identifying therapeutic targets for diseases such as cancer. The ENCODE project has mapped binding sites of many TFs in some important cell types and this project also has mapped DNase I hypersensitivity sites across the cell types. Predicting transcription factors mutual interactions would help us in finding the potential transcription regulatory networks. Here, we have developed two methods for prediction of transcription factors mutual interactions from ENCODE ChIP-seq data, and both methods generated similar results which tell us about the accuracy of the methods. It is known that functional regions of genome are conserved and here we identified that shared/overlapping transcription factor binding sites in multiple cell types and in transcription factors pairs are more conserved than their respective non-shared/non-overlapping binding sites. It has been also studied that co-binding sites influence the expression level of genes. Most of the genes mapped to the transcription factor co-binding sites have significantly higher level of expression than those genes which were mapped to the single transcription factor bound sites. The ENCODE data suggests a very large number of potential regulatory sites across the complete genome in many cell types and methods are needed to identify those that are most relevant and to connect them to the genes that they control. A penalized regression method, LASSO was used to build correlative models, and choose two regulatory regions that are predictive of gene expression, and link them to their respective gene. Here, we show that our identified regulatory regions accumulate significant number of somatic mutations that occur in cancer cells, suggesting that their effects may drive cancer initiation and development. Harboring of somatic mutations in these identified regulatory regions is an indication of positive selection, which has been also observed in cancer related genes

Oral Hygiene and Periodontal Health Status of Acute Coronary Syndrome Patients reported in PIMS Islamabad

Objective: To evaluate oral hygiene and periodontal health status of Acute Coronary Syndrome patients by using standardized oral hygiene and periodontal indices. Methodology: A cross sectional study conducted at the Cardiac center and OMFS Department of PIMS hospital Islamabad. The convenience sampling technique was used in which the sample size was calculated to be 300. Either gender, age in-between 40-75 years was included. Smokers, known diabetic, patients having any cardiac procedure <6 months, or Patients reporting periodontal treatment within 3 months were excluded. The data was analyzed by using SPSS software version 23.0. The frequencies and percentages were calculated for categorical variables and mean and standard deviation for continuous variables. Results: In this study 51% were male and 49% were female. The mean age was 54.55+9.605. It was found that 56% of included participants were living in urban areas and round about 40% belongs to the middle class socioeconomically. On the basis of oral hygiene 74% of participants had poor status. Periodontal health status was also poor as the 38.0% have gingivitis and pocket formation. Conclusion: In our study majority of acute coronary syndrome patients reported poor oral hygiene and periodontal health status although it is not clear how oral hygiene and poor periodontal health effects cardiovascular changes. To find out the association of cardiovascular disease and periodontal disease and further details of pathogenesis there is much need for clinical evidence based studies.

Drinking water quality in Rohri City, Sindh, Pakistan

Groundwater and surface water samples from Rohri city were analyzed for the presence of total coliform (TC), E. coli (Ec) and heterotrophic plate count (HPC). The samples were collected before and after storage. The bacteriological analysis was carried out by membrane filtration and spread plate count (SPC) technique. The pre-storage ground water samples were found to be contaminated with TC (25%), Ec (12.5%) and HPC (45%). All post-storage groundwater samples were found to be contaminated with TC (100%), Ec (41.6%) and with HPC (100%); the number of TC, Ec and HPC in post-storage groundwater samples was very high. The difference in number of colony forming units (cfu/100ml) between pre and post-storage groundwater samples was significant (p= 0.0001). The pre-storage surface water samples from main storage reservoirs and post-storage surface water samples from households were also found to be contaminated with TC (100%), Ec (100%) and HPC (100%). A significant (p= 0.002) difference in the number of cfu/ 100ml of ground water and in surface water samples was recorded. The quality of surface water was very poor as compared to groundwater in terms of microbial content and further declined after storage indicating lack of hygiene in the study  populationKey words: Groundwater, households, gastroenteritis and waterborne

Evaluation of Vibrio cholerae O1 El Tor variants circulating in Sindh Pakistan

Objective: To investigate the existence of genetically diverse vibrio cholerae variant strains in a rural Sindh district, and to find out the phylogenetic relationship of indigenous vibrio cholerae strains. Methods: The cross-sectional study was conducted from April 2014 to May 2016 in Khairpur, Pakistan, and comprised stool samples/rectal swabs collected from the main and city branches of the Khairpur Medical College Teaching Hospital, and the Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat. The samples were identified using standard microbiological, biochemical, serological techniques and polymerase chain reaction targeting the ompW gene. Whole genome sequencing and bioinformatics tool MUMmer 3.2.3 was used to compare indigenous and contemporary vibrio cholerae strains circulating in the province of Sindh. Neighbour-joining tree method was used to construct the phylogenic tree. Results: Of the 360 samples, 76(21.11%) were found positive for vibrio cholera strains. The species-specific ompW gene was amplified at the correct size of 588bp. The isolates belonged to serogroup Inaba, O1, biotype El Tor.  Unique sequences with same genomic coordinates showed that test strains were not similar to the reference sequence. Conserved genome sequences showed that 12 Out of 16 (75%) of the test strains were similar to each Other except the 3 strains isolated from Khairpur and 1 from Karachi. Multiple sequence alignment of the regions translated into protein showed that 13 out of 16 (81.25%) test strains were similar except 2 strains from Khairpur and 1 From Karachi. The phylogenetic tree showed that all isolated strains descended from the same ancestor along with the reference strain. Conclusions: Vibrio cholerae O1 El Tor variant existed in Khairpur. Key Words: Cholera, Vibrio cholerae, Variant, Khairpur, Phylogeny, MUMmer

Attitudes towards vaccines and intention to vaccinate against COVID-19: a cross-sectional analysis - implications for public health communications in Australia

Objective To examine SARS-CoV-2 vaccine confidence, attitudes and intentions in Australian adults as part of the iCARE Study. Design and setting Cross-sectional online survey conducted when free COVID-19 vaccinations first became available in Australia in February 2021. Participants Total of 1166 Australians from general population aged 18-90 years (mean 52, SD of 19). Main outcome measures Primary outcome: responses to question € If a vaccine for COVID-19 were available today, what is the likelihood that you would get vaccinated?'. Secondary outcome: analyses of putative drivers of uptake, including vaccine confidence, socioeconomic status and sources of trust, derived from multiple survey questions. Results Seventy-eight per cent reported being likely to receive a SARS-CoV-2 vaccine. Higher SARS-CoV-2 vaccine intentions were associated with: increasing age (OR: 2.01 (95% CI 1.77 to 2.77)), being male (1.37 (95% CI 1.08 to 1.72)), residing in least disadvantaged area quintile (2.27 (95% CI 1.53 to 3.37)) and a self-perceived high risk of getting COVID-19 (1.52 (95% CI 1.08 to 2.14)). However, 72% did not believe they were at a high risk of getting COVID-19. Findings regarding vaccines in general were similar except there were no sex differences. For both the SARS-CoV-2 vaccine and vaccines in general, there were no differences in intentions to vaccinate as a function of education level, perceived income level and rurality. Knowing that the vaccine is safe and effective and that getting vaccinated will protect others, trusting the company that made it and vaccination recommended by a doctor were reported to influence a large proportion of the study cohort to uptake the SARS-CoV-2 vaccine. Seventy-eight per cent reported the intent to continue engaging in virus-protecting behaviours (mask wearing, social distancing, etc) postvaccine. Conclusions Most Australians are likely to receive a SARS-CoV-2 vaccine. Key influencing factors identified (eg, knowing vaccine is safe and effective, and doctor's recommendation to get vaccinated) can inform public health messaging to enhance vaccination rates