Roles of trans and cis variation in yeast intraspecies evolution of gene expression.

Both cis and trans mutations contribute to gene expression divergence within and between species. We used Saccharomyces cerevisiae as a model organism to estimate the relative contributions of cis and trans variations to the expression divergence between a laboratory (BY) and a wild (RM) strain of yeast. We examined whether genes regulated by a single transcription factor (TF; single input module, SIM genes) or genes regulated by multiple TFs (multiple input module, MIM genes) are more susceptible to trans variation. Because a SIM gene is regulated by a single immediate upstream TF, the chance for a change to occur in its trans-acting factors would, on average, be smaller than that for a MIM gene. We chose 232 genes that exhibited expression divergence between BY and RM to test this hypothesis. We examined the expression patterns of these genes in a BY-RM coculture system and in a BY-RM diploid hybrid. We found that trans variation is far more important than cis variation for expression divergence between the two strains. However, because in 75% of the genes studied, cis variation has significantly contributed to expression divergence, cis change also plays a significant role in intraspecific expression evolution. Interestingly, we found that the proportion of genes with diverged expression between BY and RM is larger for MIM genes than for SIM genes; in fact, the proportion tends to increase with the number of transcription factors that regulate the gene. Moreover, MIM genes are, on average, subject to stronger trans effects than SIM genes, though the difference between the two types of genes is not conspicuous.

The core pattern of Chinese herbal formulae and drug-herb concurrent usage in patients with dementia.

More than 40% dementia patients received traditional Chinese Medicine treatment. However, the prescription pattern of Chinese herbal formulae (CHF) for treating neurocognitive or behavioral disorders in patients with dementia has not been elucidated. This large-scale survey aimed is to evaluate core patterns of CHF and drug-herb concurrent use in patients with dementia.We analyzed patients with a diagnosis of dementia from one million cohorts of the Longitudinal Health Insurance Database in the National Health Insurance Research Database, between 1997 and 2008. Of 18,141 newly diagnosed dementia patients, 3471 patients received CHF for mental and nervous system diseases. There were 13,254 outpatient visits, with 60,968 formulae prescriptions. We calculate the frequency and proportion of combined use, identify drug-herb concurrent usage, and determine core prescription patterns. Also, we drew network graphs of co-prescription pairs which occurred more than 200 times.Chinese medicine prescription patterns changed as dementia progressed.During the first 3 years after the diagnosis of dementia, Jia-Wei-Xiao-Yao-San, Gan-Mai-Da-Zao-Tang, and Ban-Xia-Bai-Zhu-Tian-Ma-Tang were the core CHF prescribed for mental and nervous system disorders. However, during the later stages of dementia, Suan-Zao-Ren-Tang, Gui-Pi-Tang, Jia-Wei-Xiao-Yao-San, and Wen-Dan-Tang were the core CHF prescribed. Benzodiazepines were the most common sedative drugs combined with traditional Chinese formulae.The results of this study suggest that TCM prescription were different in various stages of dementia, and indicated the frequently combined use of the TCM formulae and Benzodiazepines in dementia care.

Multidimensional scaling for large genomic data sets.

BACKGROUND: Multi-dimensional scaling (MDS) is aimed to represent high dimensional data in a low dimensional space with preservation of the similarities between data points. This reduction in dimensionality is crucial for analyzing and revealing the genuine structure hidden in the data. For noisy data, dimension reduction can effectively reduce the effect of noise on the embedded structure. For large data set, dimension reduction can effectively reduce information retrieval complexity. Thus, MDS techniques are used in many applications of data mining and gene network research. However, although there have been a number of studies that applied MDS techniques to genomics research, the number of analyzed data points was restricted by the high computational complexity of MDS. In general, a non-metric MDS method is faster than a metric MDS, but it does not preserve the true relationships. The computational complexity of most metric MDS methods is over O(N2), so that it is difficult to process a data set of a large number of genes N, such as in the case of whole genome microarray data. RESULTS: We developed a new rapid metric MDS method with a low computational complexity, making metric MDS applicable for large data sets. Computer simulation showed that the new method of split-and-combine MDS (SC-MDS) is fast, accurate and efficient. Our empirical studies using microarray data on the yeast cell cycle showed that the performance of K-means in the reduced dimensional space is similar to or slightly better than that of K-means in the original space, but about three times faster to obtain the clustering results. Our clustering results using SC-MDS are more stable than those in the original space. Hence, the proposed SC-MDS is useful for analyzing whole genome data. CONCLUSION: Our new method reduces the computational complexity from O(N3) to O(N) when the dimension of the feature space is far less than the number of genes N, and it successfully reconstructs the low dimensional representation as does the classical MDS. Its performance depends on the grouping method and the minimal number of the intersection points between groups. Feasible methods for grouping methods are suggested; each group must contain both neighboring and far apart data points. Our method can represent high dimensional large data set in a low dimensional space not only efficiently but also effectively.

Enhancing image watermarking methods with/without reference images by optimization on second-order statistics.

The watermarking method has emerged as an important tool for content tracing, authentication, and data hiding in multimedia applications. We propose a watermarking strategy in which the watermark of a host is selected from the robust features of the estimated forged images of the host. The forged images are obtained from Monte Carlo simulations of potential pirate attacks on the host image. The solution of applying an optimization technique to the second-order statistics of the features of the forged images gives two orthogonal spaces. One of them characterizes most of the variations in the modifications of the host. Our watermark is embedded in the other space that most potential pirate attacks do not touch. Thus, the embedded watermark is robust. Our watermarking method uses the same framework for watermark detection with a reference and blind detection. We demonstrate the performance of our method under various levels of attacks.

Effects of cis and trans regulatory variations on the expression divergence of heat shock response genes between yeast strains.

Phenotypic variation among individuals in a population can be due to DNA sequence variation in protein coding regions or in regulatory elements. Recently, many studies have indicated that mutations in regulatory elements may be the major cause of phenotypic evolution. However, the mechanisms for evolutionary changes in gene expression are still not well understood. Here, we studied the relative roles of cis and trans regulatory changes in Saccharomyces cerevisiae cells to cope with heat stress. It has been found that the expression level of ~300 genes was induced at least two fold and that of ~500 genes was repressed at least two fold in response to heat shock. From the former set of genes, we randomly selected 65 genes that showed polymorphism(s) between the BY and RM strains for pyrosequencing analysis to explore the relative contributions of cis and trans regulatory variations to the expression divergence between BY and RM. Our data indicated that the expression divergence between BY and RM was mainly due to trans regulatory variations under either the normal condition or the heat stress condition. However, the relative contribution of trans regulatory variation was decreased from 76.9% to 61.5% after the heat shock stress. These results indicated that the cis regulatory variation may play an important role in the adaption to heat stress. In our data, 43.1% (28 genes) of the 65 genes showed the same trend of cis or trans variation effect after the heat shock stress, 35.4% (23 genes) showed an increased cis variation effect and 21.5% (14 genes) showed an increased trans variation effect after the heat shock stress. Thus, our data give insights into the relative roles of cis and trans variations in response to heat shock in yeast.

Prescription profile of Chinese herbal products containing coumestrol, genestein, and/or daidzein among female users: an analysis of national health insurance data in Taiwan between 1997 and 2007.

BACKGROUND: Some Chinese herbs contain several kinds of phytoestrogens, and these herbs are commonly prescribed in Taiwan. Phytoestrogens may influence the effects of estrogen in females, although their activities are weak. This study aims to identify the risk and analyze the prescription profile of commonly used phytoestrogenic herbs in Taiwan. METHODS: The study analyzed women who had been prescribed phytoestrogenic herbs including coumestrol, genistein and/or daidzein between 1997 and 2007 in a fixed cohort taken from all female beneficiaries from the National Health Insurance Research Database of Taiwan. The prescription frequencies, cumulated dosages, and primary indications were listed. RESULTS: A total of 462,861 women were included in the study, of whom ~47.0% had used phytoestrogenic herbs at least once during the study period. A total of 6,270,813 prescriptions were recorded, and more than 20% of these contained phytoestrogens. The most commonly prescribed herb and formula were Puerariae Radix and Ge gen tang (Pueraria Decoction), respectively. Most of the prescriptions were issued for diseases of the respiratory system, followed by symptoms, signs, and ill-defined conditions and diseases of the musculoskeletal system and connective tissue. CONCLUSION: This study shows that women who sought medical treatment from Chinese medicine doctors for relief of respiratory discomfort had a high possibility of exposure to phytoestrogenic herbs. Safety issues related to the female endocrine system should be a priority for future research.