Correlating gene and protein expression data using Correlated Factor Analysis

<p>Abstract</p> <p>Background</p> <p>Joint analysis of transcriptomic and proteomic data taken from the same samples has the potential to elucidate complex biological mechanisms. Most current methods that integrate these datasets allow for the computation of the correlation between a gene and protein but only after a one-to-one matching of genes and proteins is done. However, genes and proteins are connected via biological pathways and their relationship is not necessarily one-to-one. In this paper, we investigate the use of Correlated Factor Analysis (CFA) for modeling the correlation of genome-scale gene and protein data. Unlike existing approaches, CFA considers all possible gene-protein pairs and utilizes all gene and protein information in its modeling framework. The Generalized Singular Value Decomposition (gSVD) is another method which takes into account all available transcriptomic and proteomic data. Comparison is made between CFA and gSVD.</p> <p>Results</p> <p>Our simulation study indicates that the CFA estimates can consistently capture the dominant patterns of correlation between two sets of measurements; in contrast, the gSVD estimates cannot do that. Applied to real cancer data, the list of co-regulated genes and proteins identified by CFA has biologically meaningful interpretation, where both the gene and protein expressions are pointing to the same processes. Among the GO terms for which the genes and proteins are most correlated, we observed blood vessel morphogenesis and development.</p> <p>Conclusion</p> <p>We demonstrate that CFA is a useful tool for gene-protein data integration and modeling, where the main question is in finding which patterns of gene expression are most correlated with protein expression.</p

Identification of recurrent regions of copy-number variants across multiple individuals

10.1186/1471-2105-11-147BMC Bioinformatics1

Possible Influence of δ-Aminolevulinic Acid Dehydratase Polymorphism and Susceptibility to Renal Toxicity of Lead: A Study of a Vietnamese Population

We examined six newly identified polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) single-nucleotide polymorphisms (SNPs) to determine if these SNPs could modify the relationship between blood lead (PbB) and some renal parameters. This is a cross-sectional study of 276 lead-exposed workers in Vietnam. All workers were measured for PbB, urinary retinol-binding protein (URBP), urinary α(1)-microglobulin (Uα1m), urinary β(2)-microglobulin (Uβ2m), urinary N-acetyl-β-d-glucosaminidase (NAG), urinary aminolevulinic acid (ALAU), serum α(1)-microglobulin (Sα1m), serum β(2)-microglobulin (Sβ2m), and urinary albumin (Ualb). The six SNPs were Msp and Rsa in exon 4, Rsa39488 in exon 5, HpyIV and HpyCH4 in intron 6, and Sau3A in intron 12. Analysis of covariance (ANCOVA) with interaction of PbB × SNPs were applied to examine modifying effect of the SNPs on the association of renal parameters and PbB, adjusting for potential confounders of age, gender, body mass index, and exposure duration. HpyCH4 was found to be associated with certain renal parameters. For HpyCH4 1-1, an increase of 1 μg/dL PbB caused an increase of 1.042 mg/g creatinine (Cr) Uα1m, 1.069 mg/g Cr Uβ2m, 1.038 mg/g Cr URBP, and 1.033 mg/g Cr Ualb, whereas in HpyCH4 1-2, an increase of 1 μg/dL PbB resulted in an increase of only 1.009 mg/g Cr Uα1m, 1.012 mg/g Cr Uβ2m, 1.009 mg/g Cr URBP, and 1.007 mg/g Cr Ualb. HpyCH4 SNP appeared to modify the lead toxicity to kidney with wild-type allele being more susceptible than variants. The mechanism for this effect is not clear. Further studies are needed to confirm this observation

Health systems reforms in Singapore: A qualitative study of key stakeholders.

In response to a growing chronic disease burden and ageing population, Singapore implemented Regional Health Systems (RHS) in 2008. In January 2017, the MOH announced that the six RHS clusters would be reorganised into three in 2018. This qualitative study sought to identify the health system challenges, opportunities, and ways forward for the implementation of the RHS. We conducted semi-structured interviews with 35 key informants from RHS clusters, government, academia, and private and voluntary sectors. Integration, innovation, and people-centeredness were identified as the key principles of the RHS. The RHS was described as an opportunity to holistically care for a person across the care continuum, address social determinants of health, develop new models of care, and work with social and community partners. Challenges to RHS implementation included difficulties aligning the goals, values, and priorities of multiple actors, the need for better integration across clusters, differing care capabilities and capacities across partners, healthcare financing structures that may not reflect RHS goals, scalability and evaluation of pilot programmes, and disease-centricity, provider-centricity, and medicalisation in health and healthcare. Suggested ways forward included building relationships between actors to facilitate integration; exploring innovative new models of care; clear long-term/scale-up plans for successful pilots; healthcare financing reforms to meet changing patient and population needs; and developing evaluation systems reflective of RHS principles and priorities

Assessing the influence of health systems on Type 2 Diabetes Mellitus awareness, treatment, adherence, and control: A systematic review.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is reported to affect one in 11 adults worldwide, with over 80% of T2DM patients residing in low-to-middle-income countries. Health systems play an integral role in responding to this increasing global prevalence, and are key to ensuring effective diabetes management. We conducted a systematic review to examine the health system-level factors influencing T2DM awareness, treatment, adherence, and control. METHODS AND FINDINGS: A protocol for this study was published on the PROSPERO international prospective register of systematic reviews (PROSPERO 2016: CRD42016048185). Studies included in this review reported the effects of health systems factors, interventions, policies, or programmes on T2DM control, awareness, treatment, and adherence. The following databases were searched on 22 February 2017: Medline, Embase, Global health, LILACS, Africa-Wide, IMSEAR, IMEMR, and WPRIM. There were no restrictions on date, language, or study designs. Two reviewers independently screened studies for eligibility, extracted the data, and screened for risk of bias. Thereafter, we performed a narrative synthesis. A meta-analysis was not conducted due to methodological heterogeneity across different aspects of included studies. 93 studies were included for qualitative synthesis; 7 were conducted in LMICs. Through this review, we found two key health system barriers to effective T2DM care and management: financial constraints faced by the patient and limited access to health services and medication. We also found three health system factors that facilitate effective T2DM care and management: the use of innovative care models, increased pharmacist involvement in care delivery, and education programmes led by healthcare professionals. CONCLUSIONS: This review points to the importance of reducing, or possibly eliminating, out-of-pocket costs for diabetes medication and self-monitoring supplies. It also points to the potential of adopting more innovative and integrated models of care, and the value of task-sharing of care with pharmacists. More studies which identify the effect of health system arrangements on various outcomes, particularly awareness, are needed

Rural and urban differences in health system performance among older Chinese adults : Cross-sectional analysis of a national sample

Background: Despite improvement in health outcomes over the past few decades, China still experiences striking rural-urban health inequalities. There is limited research on the rural-urban differences in health system performance in China. Method: We conducted a cross-sectional analysis to compare health system performance between rural and urban areas in five key domains of the health system: effectiveness, cost, access, patient-centredness and equity, using data from the WHO Study on Global AGEing and adult health (SAGE), China. Multiple logistic and linear regression models were used to assess the first four domains, adjusting for individual characteristics, and a relative index of inequality (RII) was used to measure the equity domain. Findings: Compared to urban areas, rural areas had poorer performance in the management and control of hypertension and diabetes, with more than 50% lower odds of having breast (AOR = 0.44; 95% CI: 0.30, 0.64) and cervical cancer screening (AOR = 0.49; 95% CI: 0.29, 0.83). There was better performance in rural areas in the patient-centredness domain, with more than twice higher odds of getting prompt attention, respect, clarity of the communication with health provider and involvement in decision making of the treatment in inpatient care (AOR = 2.56, 2.15, 2.28, 2.28). Although rural residents incurred relatively less out-of-pocket expenditures (OOPE) for outpatient and inpatient services than urban residents, they were more likely to incur catastrophic expenditures on health (AOR = 1.30; 95% CI 1.16, 1.44). Wealth inequality was found in many indicators related to the effectiveness, costs and access domains in both rural and urban areas. Rural areas had greater inequalities in the management of hypertension and coverage of cervical cancer (RII = 7.45 vs 1.64). Conclusion: Our findings suggest that urban areas have achieved better prevention and management of non-communicable disease than rural areas, but access to healthcare was equivalent. A better understanding of the causes of the observed variations is needed to develop appropriate policy interventions which address these disparities

Community participation in health services development, implementation, and evaluation: A systematic review of empowerment, health, community, and process outcomes.

BACKGROUND: Community participation is widely believed to be beneficial to the development, implementation and evaluation of health services. However, many challenges to successful and sustainable community involvement remain. Importantly, there is little evidence on the effect of community participation in terms of outcomes at both the community and individual level. Our systematic review seeks to examine the evidence on outcomes of community participation in high and upper-middle income countries. METHODS AND FINDINGS: This review was developed according to PRISMA guidelines. Eligible studies included those that involved the community, service users, consumers, households, patients, public and their representatives in the development, implementation, and evaluation of health services, policy or interventions. We searched the following databases from January 2000 to September 2016: Medline, Embase, Global Health, Scopus, and LILACs. We independently screened articles for inclusion, conducted data extraction, and assessed studies for risk of bias. No language restrictions were made. 27,232 records were identified, with 23,468 after removal of duplicates. Following titles and abstracts screening, 49 met the inclusion criteria for this review. A narrative synthesis of the findings was conducted. Outcomes were categorised as process outcomes, community outcomes, health outcomes, empowerment and stakeholder perspectives. Our review reports a breadth of evidence that community involvement has a positive impact on health, particularly when substantiated by strong organisational and community processes. This is in line with the notion that participatory approaches and positive outcomes including community empowerment and health improvements do not occur in a linear progression, but instead consists of complex processes influenced by an array of social and cultural factors. CONCLUSION: This review adds to the evidence base supporting the effectiveness of community participation in yielding positive outcomes at the organizational, community and individual level. TRIAL REGISTRATION: Prospero record number: CRD42016048244

Secondary Household Transmission of SARS, Singapore

Secondary household transmission of severe acute respiratory syndrome (SARS) was studied in 114 households involving 417 contacts. The attack rate was low (6.2%). Occupation of the index case was the factor that most influenced household transmission (adjusted hazard ratio for healthcare workers 0.157; 95% confidence interval 0.042 to 0.588)

Incidence, mortality and survival patterns of prostate cancer among residents in Singapore from 1968 to 2002

<p>Abstract</p> <p>Background</p> <p>From 1968 to 2002, Singapore experienced an almost four-fold increase in prostate cancer incidence. This paper examines the incidence, mortality and survival patterns for prostate cancer among all residents in Singapore from 1968 to 2002.</p> <p>Methods</p> <p>This is a retrospective population-based cohort study including all prostate cancer cases aged over 20 (n = 3613) reported to the Singapore Cancer Registry from 1968 to 2002. Age-standardized incidence, mortality rates and 5-year Relative Survival Ratios (RSRs) were obtained for each 5-year period. Follow-up was ascertained by matching with the National Death Register until 2002. A weighted linear regression was performed on the log-transformed age-standardized incidence and mortality rates over period.</p> <p>Results</p> <p>The percentage increase in the age-standardized incidence rate per year was 5.0%, 5.6%, 4.0% and 1.9% for all residents, Chinese, Malays and Indians respectively. The percentage increase in age-standardized mortality rate per year was 5.7%, 6.0%, 6.6% and 2.5% for all residents, Chinese, Malays and Indians respectively. When all Singapore residents were considered, the RSRs for prostate cancer were fairly constant across the study period with slight improvement from 1995 onwards among the Chinese.</p> <p>Conclusion</p> <p>Ethnic differences in prostate cancer incidence, mortality and survival patterns were observed. There has been a substantial improvement in RSRs since the 1990s for the Chinese.</p