Cancer risk prediction with next generation sequencing data using machine learning

The use of computational biology for next generation sequencing (NGS) analysis is rapidly increasing in genomics research. However, the effectiveness of NGS data to predict disease abundance is yet unclear. This research investigates the problem in the whole exome NGS data of the chronic lymphocytic leukemia (CLL) available at dbGaP. Initially, raw reads from samples are aligned to the human reference genome using burrows wheeler aligner. From the samples, structural variants, namely, Single Nucleotide Polymorphism (SNP) and Insertion Deletion (INDEL) are identified and are filtered using SAMtools as well as with Genome Analyzer Tool Kit (GATK). Subsequently, the variants are encoded and feature selection is performed with the Pearson correlation coefficient (PCC) and the chi-square 2-df statistical test. Finally, 90:10 cross validation is performed by applying the support vector machine algorithm on sets of top selected features. It is found that the variants detected with SAMtools and GATK achieve similar prediction accuracies. It is also noted that the features that are ranked with the PCC yield better accuracy than the chi-square test. In all of the analyses, the SNPs are identified to have superior accuracy as compared to the INDELs or the full dataset. Later, an exome capture kit is introduced for analysis. The SNPs, ranked with the PCC, along with the exome capture kit yield prediction accuracy of 85.1 % and area under curve of 0.94. Overall, this study shows the effective application of the machine learning methods and the strength of the NGS data for the CLL risk prediction

Biosynthesis of vitamins and enzymes in fermented foods by lactic acid bacteria and related genera - A promising approach

Lactic acid bacteria (LAB) are widely employed in food fermentation processes for the biosynthesis of certain important products or metabolites. Fermented food provides plenty of vital nutrients and bioactive components that affect a number of functions of human body in a positive way. Fermented milks can be made more functional by incorporating probiotic strains and furthermore, if they are capable of synthesizing essential biomolecules such as vitamins, enzymes, exopolysaccharides, bacteriocins or bioactive peptides serve into the functional and technological properties of the products. Current paper reviews recent advances associated with biosynthesis of vitamins and enzymes by virtue of LAB and related genera. The outcomes of several studies indicate promising applications at commercial level; however adequate selection of strain is vital to increase the concentration and bioavailability of such biomolecules in fermented foods

Evidence-Based Assessment of Congenital Heart Disease Genes to Enable Returning Results in a Genomic Study

Background: Congenital heart disease (CHD) is the most common major congenital anomaly and causes significant morbidity and mortality. Epidemiologic evidence supports a role of genetics in the development of CHD. Genetic diagnoses can inform prognosis and clinical management. However, genetic testing is not standardized among individuals with CHD. We sought to develop a list of validated CHD genes using established methods and to evaluate the process of returning genetic results to research participants in a large genomic study. Methods: Two-hundred ninety-five candidate CHD genes were evaluated using a ClinGen framework. Sequence and copy number variants involving genes in the CHD gene list were analyzed in Pediatric Cardiac Genomics Consortium participants. Pathogenic/likely pathogenic results were confirmed on a new sample in a clinical laboratory improvement amendments-certified laboratory and disclosed to eligible participants. Adult probands and parents of probands who received results were asked to complete a post-disclosure survey. Results: A total of 99 genes had a strong or definitive clinical validity classification. Diagnostic yields for copy number variants and exome sequencing were 1.8% and 3.8%, respectively. Thirty-one probands completed clinical laboratory improvement amendments-confirmation and received results. Participants who completed postdisclosure surveys reported high personal utility and no decision regret after receiving genetic results. Conclusions: The application of ClinGen criteria to CHD candidate genes yielded a list that can be used to interpret clinical genetic testing for CHD. Applying this gene list to one of the largest research cohorts of CHD participants provides a lower bound for the yield of genetic testing in CHD

Electrospinning of Core-Shell Fibers for Encapsulation of Biomolecules

Axonal regeneration, particularly that of the neurons found in the Central Nervous System, is of great interest in tissue engineering. Diseases due to damaged nerves found in this system include Alzheimer’s, Parkinson’s and even paralysis. These affect millions of people. One way to achieve axonal regeneration is to use NGF (Nerve Growth Factors) that can guide the 2 ends of the damaged nerve into rejoining and potentially cure diseases that arise from this. The main issue is having a vessel that can produce controlled release of these NGF. One potential solution is to make a core-shell fiber, from the co-axial electro-spinning process, with the NGF incorporated in the core and PLGA (polylactic-co-glycolic-acid) acting as the shell. PLGA is biocompatible and biodegradable, making it suitable for this role. This structure could allow for a more controlled release of NGF and provides a shape that promotes axonal regeneration in the Central Nervous System. Such a structure was made in this paper with PLGA as a shell and BSA (an NGF substitute) present in the core.Biomedical Engineering, Department o

Clinical application of probiotics in the treatment of Helicobacter pylori infection—A brief review

The role of probiotics in the treatment of gastrointestinal infections is increasingly being documented as an alternative or complement to antibiotics, with the potential to decrease the use of antibiotics or reduce their side effects. Although antibiotics-based Helicobacter pylori eradication treatment is 90% effective, it is expensive and causes antibiotic resistance associated with other adverse effects. Probiotics have an in vitro inhibitory effect on H. pylori. Animal studies demonstrated that probiotic treatment is effective in reducing H. pylori-associated gastric inflammation. About 12 human studies investigated the efficacy of combinations of antibiotics and probiotics, whereas 16 studies used probiotic alone as an alternative to antibiotics for the treatment of H. pylori infection. Most of the studies showed an improvement of H. pylori gastritis and decrease in H. pylori colonization after administration of probiotics. However, no study could demonstrate complete eradication of H. pylori infection by probiotic treatment. Probiotic combinations can reduce adverse effects induced by H. pylori eradication treatment and, thus, have beneficial effects in H. pylori-infected individuals. Long-term intakes of products containing probiotic strains may have a favorable effect on H. pylori infection in humans, particularly by reducing the risk of developing disorders associated with high degrees of gastric inflammation

Determination of an antimicrobial activity of Weissella confusa, Lactobacillus fermentum, and Lactobacillus plantarum against clinical pathogenic strains of Escherichia coli and Staphylococcus aureus in co-culture

Lactic acid bacteria (LAB) have long been used to produce safe and high quality products as they are potential producers of a wide range of antimicrobial compounds that exert either narrow or wide spectrum antimicrobial activity towards spoilage or disease-causing organisms. The present investigation aimed to study the antimicrobial effect of three LAB strains, viz., Lactobacillus plantarum (86), Lactobacillus fermentum (AI2) and Weissella confusa (AI10), against two clinical pathogenic strains viz., Escherichia coli NG 502121 and Staphylococcus aureus AY 507047 in co-culture. Effects of change in inoculum size, and growth measurement at different time intervals were also studied. The pH and viable count were measured for initial as well as 24 h incubated samples. A significant (P < 0.05) reduction (2–3 log cycles) in growth of both pathogens while co-cultured with LAB strains was observed. The nonsignificant (P < 0.05) pH difference revealed the action of other metabolites apart from organic acids. LAB strains overruled the growth of E. coli and S. aureus within 10 and 6 h of the initial growth stage, respectively, compared to controls. These results led us to further characterize and purify the antimicrobial compound produced by the studied strains, so that they can be exploited in the production of safe foods with longer shelf life

Evidence for xylooligosaccharides utilization in Weissella strains isolated from Indian fermented foods and vegetables.

Six strains isolated from fermented food were by 16S rDNA sequencing identified as Weissella species, clustering with the species-pair W. confusa/ W. cibaria. The strains were analysed for growth on glucose, xylose and xylooligosaccharides (XOS). All strains were xylose positive using the API CHL 50 test. Growth on XOS was observed for strain 85, 92, 145 and AV1, firstly by optical density measurements in microtiter plates and secondly in batch cultures also confirming concomitant decrease in pH. Analysis of XOS before and after growth established consumption in the DP2 - DP5 range in the four XOS-fermenting strains. XOS were consumed simultaneously with glucose, while xylose was consumed after glucose depletion. Cell-associated β-xylosidase activity was detected in the XOS fermenting strains. Analysis of genomic data suggests this activity to be linked to genes encoding glycoside hydrolases from family 3, 8 or 43. No endo-β-xylanase activity was detectable. Main fermentation end products were lactate and acetate. A higher ratio of acetic acid/lactic acid was produced during growth on XOS compared to growth on glucose. This is the first report on utilization of XOS in Weissella, indicating an increased probiotic potential for XOS-utilizing strains from the species pair W. confusa/ W. cibaria, but also showing that XOS utilization is strain-dependent for these species. This article is protected by copyright. All rights reserved

A survey of rare epigenetic variation in 23,116 human genomes identifies disease-relevant epivariations and CGG expansions

There is growing recognition that epivariations, most often recognized as promoter hypermethylation events that lead to gene silencing, are associated with a number of human diseases. However, little information exists on the prevalence and distribution of rare epigenetic variation in the human population. In order to address this, we performed a survey of methylation profiles from 23,116 individuals using the Illumina 450k array. Using a robust outlier approach, we identified 4,452 unique autosomal epivariations, including potentially inactivating promoter methylation events at 384 genes linked to human disease. For example, we observed promoter hypermethylation of BRCA1 and LDLR at population frequencies of ∼1 in 3,000 and ∼1 in 6,000, respectively, suggesting that epivariations may underlie a fraction of human disease which would be missed by purely sequence-based approaches. Using expression data, we confirmed that many epivariations are associated with outlier gene expression. Analysis of variation data and monozygous twin pairs suggests that approximately two-thirds of epivariations segregate in the population secondary to underlying sequence mutations, while one-third are likely sporadic events that occur post-zygotically. We identified 25 loci where rare hypermethylation coincided with the presence of an unstable CGG tandem repeat, validated the presence of CGG expansions at several loci, and identified the putative molecular defect underlying most of the known folate-sensitive fragile sites in the genome. Our study provides a catalog of rare epigenetic changes in the human genome, gives insight into the underlying origins and consequences of epivariations, and identifies many hypermethylated CGG repeat expansions