HCF-CRS: A Hybrid Content based Fuzzy Conformal Recommender System for providing recommendations with confidence

A Recommender System (RS) is an intelligent system that assists users in finding the items of their interest (e.g. books, movies, music) by preventing them to go through huge piles of data available online. In an effort to overcome the data sparsity issue in recommender systems, this research incorporates a content based filtering technique with fuzzy inference system and a conformal prediction approach introducing a new framework called Hybrid Content based Fuzzy Conformal Recommender System (HCF-CRS). The proposed framework is implemented to be used in the domain of movies and it provides quality recommendations to users with a confidence level and an improved accuracy. In our proposed framework, first, a Content Based Filtering (CBF) technique is applied to create a user profile by considering the history of each user. CBF is useful in the situations like: lack of demographic information and the data sparsity problems. Second, a Fuzzy based technique is incorporated to find the similarities and differences between the user profile and the movies in the dataset using a set of fuzzy rules to get a predicted rating for each movie. Third, a Conformal prediction algorithm is implemented to calculate the non-conformity measure between the predicted ratings produced by fuzzy system and the actual ratings from the dataset. A p-value (confidence measure) is computed to give a level of confidence to each recommended item and a bound is set on the confidence level called a significance level ε, according to which the movies only above the specified significance level are recommended to user. By building a confidence centric hybrid conformal recommender system using the content based filtering approach with fuzzy logic and conformal prediction algorithm, the reliability and the accuracy of the system is considerably enhanced. The experiments are evaluated on MovieLens and Movie Tweetings datasets for recommending movies to the users and they are compared with other state-of-the-art recommender systems. Finally, the results confirm that the proposed algorithms perform better than the traditional ones

MTHFR gene C677T and A1298C polymorphisms and homocysteine levels in primary open angle and primary closed angle glaucoma

Contains fulltext : 79920.pdf (publisher's version ) (Open Access)PURPOSE: To investigate the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genotypes and plasma concentrations of total homocysteine (tHcy) in Pakistani patients with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG). METHODS: This was a prospective case-control study. A total of 295 patients (173 POAG, 122 PCAG) and 143 age- and sex-matched controls were subdivided into two ethnic groups, Punjabis (Punjab province, central Pakistan) and Pathans (North-West Frontier Province, northern Pakistan). Genotypes of the MTHFR C677T and A1298C polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An enzyme-linked immunosorbent assay was used to determine the total serum homocysteine (tHcy) levels. Associations were determined by logistic regression analysis. RESULTS: Frequency distributions of genotypes and combined genotypes as well as homocysteine levels were obtained. The overall distribution of the C677T genotype was found to be significantly associated with PCAG (CC 69%, CT 21%, TT 10%; p=0.001, chi(2)=12.6), but not with POAG (CC 71%, CT 28%, TT 1%; p=0.98, chi(2)=0.02) as compared to the controls (CC 71%, CT 29%, TT 1%). The Pathan cohorts revealed no association with the disease; however, the Punjabis demonstrated a significant association with PCAG (CC 75%, CT 11%, TT 13%; p<0.001, chi(2)=17.2). PCAG in the Punjabi subjects was also significantly associated with the A1298C polymorphism (AA 43%, AC 54%, CC 3%; p<0.001, chi(2)=33.9) as compared to the controls. Combined genotype data showed no association with POAG; however, a significant association with all combined genotypes was observed in the overall PCAG subjects (p<0.05, chi(2)=20.1). This difference was particularly apparent in the TTAA and TTAC combinations that were completely absent in the control groups (p<0.05. chi(2)=49.6). Mean serum tHcy levels were found to be significantly increased in the POAG (15.2+/-1.28 micromol/l, p<0.001) and PCAG (20.8+/-4.8 micromol/l) groups as compared to the controls (10.0+/-0.97 micromol/l). The tHcy levels in the TT and AC genotype were significantly elevated in the PCAG group (67+/-12.39 micromol/l, p<0.001; 23+/-5.94 micromol/l, p=0.027) as compared to the controls. CONCLUSION: The TT and AC genotypes of MTHFR C677T and A1298C polymorphisms and the combined genotype TTAC were associated with PCAG in Punjabi subjects of Pakistani origin and correlated with the high serum tHcy levels seen in these patients

The association of glutathione S-transferase GSTT1 and GSTM1 gene polymorphism with pseudoexfoliative glaucoma in a Pakistani population

Contains fulltext : 88996.pdf (publisher's version ) (Open Access)PURPOSE: The aim of the present study was to investigate the association of glutathione S-transferase GSTT1 and GSTM1 genotypes with pseudoexfoliative glaucoma (PEXG) in a group of Pakistani patients. METHODS: Multiplex polymerase chain reaction was used to study the GSTT1 and GSTM1 polymorphisms in 165 PEXG patients and 162 unaffected controls. RESULTS: In the current study we describe a significant gender-specific association of GSTT1 and GSTM1 null genotypes with PEXG. The three null genotype combinations (i.e., T1M0, T0M1, and T0M0) were found at significantly higher frequencies in the PEXG patients as compared to the controls (chi(2)=21.82, p0.05). CONCLUSIONS: The results suggest that there is a significant involvement of the GSTT1 and GSTM1 polymorphisms in female Pakistani patients having PEXG, which suggests a possible gender-specific impairment of detoxification in this group

Role of Lysyl oxidase-like 1 gene polymorphisms in Pakistani patients with pseudoexfoliative glaucoma

Contains fulltext : 109429.pdf (publisher's version ) (Open Access)PURPOSE: Single nucleotide polymorphisms (SNPs) rs1048661 (p.R141L) and rs3825942 (p.G153D) in the lysyl oxidase-like 1 (LOXL1) gene have been previously reported to be associated with pseudoexfoliation glaucoma (PEXG) in various Asian and European populations, but these SNPs have not yet been studied in the Pakistani population. Therefore the aim of the present study was to investigate the association of these two coding LOXL1 SNPs in Pakistani PEXG patients. METHODS: One hundred twenty-eight Pakistani patients diagnosed with PEXG and 180 healthy controls were recruited for the study. Genomic DNA was extracted and both SNPs were genotyped by direct sequencing. Association of genotype and allele frequencies with PEXG were analyzed using the Chi-square (chi(2)) test. RESULTS: Genotype and allele frequencies of both rs1048661 and rs3825942 were found to be significantly associated with PEXG. The GG genotypes of both LOXL1 SNPs were associated with an increased risk of developing PEXG. In addition the G alleles of rs1048661 and rs3825942 confer an increased risk for PEXG with an odds ratio (OR) of 2.98 (95% CI 1.94-4.57) and OR 6.83 (95% CI 2.94-16.67), respectively. CONCLUSIONS: A significant association was found for the G allele of rs1048661 and rs3825942 in PEXG patients of Pakistani origin

A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease

Contains fulltext : 110974.pdf (publisher's version ) (Open Access)PURPOSE: Genetic studies were performed to identify the causative mutation in a 15-year-old girl diagnosed with congenital stationary night blindness (CSNB) presenting Mizuo-Nakamura phenomenon, a typical Oguchi disease symptom. The patient also had dural sinus thrombosis (DST), thrombocytopenia, and systemic lupus erythematosus (SLE). METHODS: Mutation analysis was done by sequencing two candidate genes, S-antigen (SAG; arrestin 1), associated with Oguchi type 1, and rhodopsin kinase (GRK1), associated with Oguchi type 2. In addition, the C677T variation in the methylenetetrahydrofolate reductase (MTHFR) gene was also screened in the family, to determine its probable association with hyperhomocysteinemia in the patient. RESULTS: Sequencing of the SAG and GRK1 resulted in identifying a novel homozygous nonsense mutation (c.916G>T; p.Glu306*) in SAG, which in unaffected siblings either was present in a heterozygous state or absent. The C677T heterozygous allele in the MTHFR gene was found to be associated with hyperhomocysteinemia in the patient and other family members. CONCLUSIONS: This is the first report of Oguchi type 1 in a Pakistani patient due to a nonsense mutation (c.916G>T; p.Glu306*) in SAG. The neurologic and hematological abnormalities likely are not associated with the SAG variant

A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family

Contains fulltext : 76070.pdf (publisher's version ) (Open Access)PURPOSE: The purpose of this study was to identify the underlying molecular genetic defect in a large consanguineous Pakistani family with Oguchi disease who had been given a diagnosis of autosomal recessive retinitis pigmentosa. METHODS: The family was genotyped with the Affymetrix 10K single nucleotide polymorphism array. Fine-mapping of a common homozygous region on chromosome 13q was performed using fluorescent microsatellite markers. Mutation analysis was done by direct sequencing of the candidate gene GRK1 located in the region. The segregation of a novel mutation in the family and the frequency of the identified mutation in the Pakistani population were determined by StuI RFLP analysis. RESULTS: Genetic mapping supported the diagnosis of typical Oguchi disease in a Pakistani family and also resulted in the identification of a novel nonsense mutation (c.614C>A; p.S205X) in exon 1 of GRK1. This mutation is predicted to result in premature termination of the protein product, thereby affecting the phototransduction cascade. A clinical reappraisal of the family revealed that all patients homozygous for this variant had Oguchi disease. CONCLUSIONS: This is the first report to describe a mutation causing typical Oguchi disease in a large consanguineous Pakistani family. This mutation segregated in eight affected members.6 p

Identification of recurrent and novel mutations in TULP1 in Pakistani families with early-onset retinitis pigmentosa

Contains fulltext : 108208.pdf (publisher's version ) (Open Access)PURPOSE: To identify the genetic defects underlying retinitis pigmentosa (RP) in Pakistani families. METHODS: Genome-wide high-density single-nucleotide-polymorphism microarray analysis was performed using the DNA of nine affected individuals from two large families with multiple consanguineous marriages. Data were analyzed to identify homozygous regions that are shared by affected sibs in each family. Sanger sequencing was performed for genes previously implicated in autosomal recessive RP and allied retinal dystrophies that resided in the identified homozygous regions. Probands from both families underwent fundus examination and electroretinogram measurements. RESULTS: The tubby-like protein 1 gene (TULP1) was present in the largest homozygous region in both families. Sequence analysis identified a previously reported mutation (c.1138A>G; p.Thr380Ala) in one family and a novel pathogenic variant (c.1445G>A; p.Arg482Gln) in the other family. Both variants were found to be present in a homozygous state in all affected individuals, were heterozygous present in the unaffected parents, and heterozygous present or absent in normal individuals. Affected individuals of both families showed an early-onset form of RP. CONCLUSIONS: Homozygosity mapping, combined with candidate-gene analysis, successfully identified genetic defects in TULP1 in two large Pakistani families with early-onset retinitis pigmentosa