In the Galilean transformation system, a body contacts and moves on the moving frame and is completely carried by the moving frame and hence the body and the moving frame have the same time rule but velocity of the body moving in the... more
In the Galilean transformation system, a body contacts and moves on the moving frame and is completely carried by the moving frame and hence the body and the moving frame have the same time rule but velocity of the body moving in the stationary frame is larger than in the moving frame. In the Lorentz transformation system, however, a body is free in all frames and hence not carried by the moving frame and the body moving in the moving and stationary frames has the same velocity but different time rules. We mathematically proved that the classical Lorentz transformation works for movement of a body with light speed in all frames. Invariance of light speed in all frames is an instance of Lorentz velocity invariance. Galilean linear velocity addition can be derived from “complete carry” mechanism. We proved that Lorentz transformation cannot be reduced to Galilean transformation in any situation. A general transformation was given from “partial carry” mechanism. The general transformat...
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Source code: three R functions: BAT.R, ELS.R, simulatF2.R. (ZIP 4Â kb)
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Selecting a set of valid genetic variants is critical for Mendelian randomization (MR) to correctly infer risk factors causing a disease. We here developed a method for selecting genetic variants as valid instrumental variables for... more
Selecting a set of valid genetic variants is critical for Mendelian randomization (MR) to correctly infer risk factors causing a disease. We here developed a method for selecting genetic variants as valid instrumental variables for inferring risk factors causing coronary artery disease (CAD). Using this method, we selected two sets of single-nucleotide-polymorphism (SNP) genetic variants (SNP338 and SNP363) associated with each of the three potential risk factors for CAD including low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and triglycerides (TG) from two independent GWAS datasets. We performed in-depth multivariate MR (MVMR) analyses and the results from both datasets consistently showed that LDL-c was strongly associated with increased risk for CAD (β = 0.396,OR = 1.486 per 1 SD (equivalent to 38 mg/dL), 95CI = (1.38, 1.59) in SNP338; and β = 0.424, OR = 1.528 per 1 SD, 95%CI = (1.42, 1.65) in SNP363); HDL-c was strongly associated wit...
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Clostridium acetobutylicum is not able to grow on glycerol as the sole carbon source since it cannot reoxidize the excess of NADH generated by glycerol catabolism. Nevertheless, when the pSPD5 plasmid, carrying the NADH-consuming... more
Clostridium acetobutylicum is not able to grow on glycerol as the sole carbon source since it cannot reoxidize the excess of NADH generated by glycerol catabolism. Nevertheless, when the pSPD5 plasmid, carrying the NADH-consuming 1,3-propanediol pathway from C. butyricum VPI 3266, was introduced into C. acetobutylicum DG1, growth on glycerol was achieved, and 1,3-propanediol was produced. In order to compare the physiological behavior of the recombinant C. acetobutylicum DG1(pSPD5) strain with that of the natural 1,3-propanediol producer C. butyricum VPI 3266, both strains were grown in chemostat cultures with glycerol as the sole carbon source. The same “global behavior” was observed for both strains: 1,3-propanediol was the main fermentation product, and the qH 2 flux was very low. However, when looking at key intracellular enzyme levels, significant differences were observed. Firstly, the pathway for glycerol oxidation was different: C. butyricum uses a glycerol dehydrogenase and...
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Rapid development of transcriptome sequencing technologies has resulted in a data revolution and emergence of new approaches to study transcriptomic regulation such as alternative splicing, alternative polyadenylation, CRISPR knockout... more
Rapid development of transcriptome sequencing technologies has resulted in a data revolution and emergence of new approaches to study transcriptomic regulation such as alternative splicing, alternative polyadenylation, CRISPR knockout screening in addition to the regular gene expression. A full characterization of the transcriptional landscape of different groups of cells or tissues holds enormous potential for both basic science as well as clinical applications. Although many methods have been developed in the realm of differential gene expression analysis, they all geared towards a particular type of sequencing data and failed to perform well when applied in different types of transcriptomic data. To fill this gap, we offer a negative beta binomial t-test (NBBt-test). NBBt-test provides multiple functions to perform differential analyses of alternative splicing, polyadenylation, CRISPR knockout screening, and gene expression datasets. Both real and large-scale simulation data show...
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Background ETV6-RUNX1 is the most prevalent translocation in pediatric B-ALL (B-cell Acute Lymphoblastic Leukemia). However, the exact pathogenesis of this translocation leading to leukemogenesis remains unclear. Insulin like Growth... more
Background ETV6-RUNX1 is the most prevalent translocation in pediatric B-ALL (B-cell Acute Lymphoblastic Leukemia). However, the exact pathogenesis of this translocation leading to leukemogenesis remains unclear. Insulin like Growth Factor 2 Binding Protein 1 (IGF2BP1), an oncofetal RNA binding protein (RBP), is overexpressed in ETV6-RUNX1 positive B-ALL. We intended to investigate the role of IGF2BP1 in leukemogenesis in this study. Methods qRT-PCR was used to analyze IGF2BP1 overexpression in an Indian cohort of pediatric B-ALL (n = 167). IGF2BP1 and ETV6-RUNX1 were knocked out in Reh, an ETV6-RUNX1 positive B-ALL cell line, using CRISPR/Cas9 technology. Cell proliferation assays were used to study cell survival after IGF2BP1/ETV6-RUNX1 KO and prednisolone response. RNA-Sequencing after IGF2BP1 knockout and RNA Immunoprecipitation sequencing (RIP-Seq) after IGF2BP1 pulldown were performed to find the putative targets of IGF2BP1. Luciferase reporter assays were used to study downst...
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A hypothesis of molecular mechanism of heterosis, the concerted effect of heterozyme, was suggested in light of the relationship between function and structure of enzyme in this paper. The positive and negative concerted effects of... more
A hypothesis of molecular mechanism of heterosis, the concerted effect of heterozyme, was suggested in light of the relationship between function and structure of enzyme in this paper. The positive and negative concerted effects of heterozymes can be applied reasonably to interpret the positiveness and negativeness of heterosis and their intensity. There are many identical characters between heteroenzyme and heterosis. Active polymorphism of heterozyme has been testified by investigation of isozyme or allozyme. Many results suggested that intensity of activation of heterozyme from isozymes be highly correlated to heterosis. From the catalytic concert produced by the transfer of conformation change that results from reaction among subunits of a heterozyme.
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Volume 7(8) ISSN Abstract: Identification of genes differentially expressed across multiple conditions has become an important statistical problem in analyzing large-scale microarray data. Many statistical methods have been developed to... more
Volume 7(8) ISSN Abstract: Identification of genes differentially expressed across multiple conditions has become an important statistical problem in analyzing large-scale microarray data. Many statistical methods have been developed to address the challenging problem. Therefore, an extensive comparison among these statistical methods is extremely important for experimental scientists to choose a valid method for their data analysis. In this study, we conducted simulation studies to compare six statistical methods: the Bonferroni (B-) procedure, the Benjamini and Hochberg (BH-) procedure, the Local false discovery rate (Localfdr) method, the Optimal Discovery Procedure (ODP), the Ranking Analysis of F-statistics (RAF), and the Significant Analysis of Microarray data (SAM) in identifying differentially expressed genes. We demonstrated that the strength of treatment effect, the sample size, proportion of differentially expressed genes and variance of gene expression will significantly...
We investigate the impact of genetic variants on transiently upregulated gestational insulin signaling. We recruited 1152 unrelated nondiabetic pregnant Han Chinese women (age 28.5 ± 4.1 years; body mass index [BMI] 21.4 ± 2.6 kg/m(2))... more
We investigate the impact of genetic variants on transiently upregulated gestational insulin signaling. We recruited 1152 unrelated nondiabetic pregnant Han Chinese women (age 28.5 ± 4.1 years; body mass index [BMI] 21.4 ± 2.6 kg/m(2)) and gave them oral glucose tolerance tests. Matsuda index of insulin sensitivity, homeostatic model assessment of insulin resistance, indices of insulin disposition, early-phase insulin release, fasting state, and 0 to 120 minute's proinsulin to insulin conversion were used to dissect insulin physiological characterization. Several variants related to β-cell function were genotyped. The genetic impacts were analyzed using logistic regression under an additive model. By adjusting for maternal age, BMI, and the related interactions, the genetic variants in ABCC8, CDKAL1, CDKN2A, HNF1B, KCNJ11, and MTNR1B were detected to impact gestational insulin signaling through heterogeneous mechanisms; however, compared with that in nonpregnant metabolism, the ...
Research Interests: Biology, China, Medicine, Insulin Resistance, Pregnancy, and 15 moreHumans, Blood Glucose, Insulin, Female, Body Mass Index, Phenotype, Reproductive Sciences, Adult, Maternal Age, Asian Continental Ancestry Group, Genetic variation, Glucose Tolerance Test, Genetic Markers, Logistic Models, and Paediatrics and reproductive medicine
Next generation sequencing is being increasingly used for transcriptome-wide analysis of differential gene expression. The primary goal in profiling expression is to identify genes or RNA isoforms differentially expressed between specific... more
Next generation sequencing is being increasingly used for transcriptome-wide analysis of differential gene expression. The primary goal in profiling expression is to identify genes or RNA isoforms differentially expressed between specific conditions. Yet, the next generation sequence-based count data are essentially different from the microarray data that are continuous type, therefore, the statistical methods developed well over the last decades cannot be applicable. For this reason, a variety of new statistical methods based on count data of transcript reads has been correspondingly developed. But currently the transcriptomic count data coming only from a few replicate libraries have high technical noise and small sample size bias, performances of these new methods are not desirable. We here developed a new statistical method specifically applicable to small sample count data called mBeta t-test for identifying differentially expressed gene or isoforms on the basis of the Beta t-t...
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Next generation sequencing (NGS) is increasingly being used for transcriptome-wide analysis of differential gene expression. The NGS data are multidimensional count data. Therefore, most of the statistical methods developed well for... more
Next generation sequencing (NGS) is increasingly being used for transcriptome-wide analysis of differential gene expression. The NGS data are multidimensional count data. Therefore, most of the statistical methods developed well for microarray data analysis are not applicable to transcriptomic data. For this reason, a variety of new statistical methods based on count data of transcript reads have been correspondingly proposed. But due to high cost and limitation of biological resources, current NGS data are still generated from a few replicate libraries. Some of these existing methods do not always have desirable performances on count data. We here developed a very powerful and robust statistical method based on beta and binomial distributions. Our method (mBeta t-test) is specifically applicable to sequence count data from small samples. Both simulated and real transcriptomic data showed mBeta t-test significantly outperformed the existing top statistical methods chosen in all 12 g...
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There is a complex- and multi-effect for interdependent survival between intestinal- microorganisms and hosts. The symbiosis or coevolution that results from this effect for interdependent survival is used to reveal the phylogenies of... more
There is a complex- and multi-effect for interdependent survival between intestinal- microorganisms and hosts. The symbiosis or coevolution that results from this effect for interdependent survival is used to reveal the phylogenies of hosts as well as intestinal microorganisms. The symbiosis or coevolution between intestinal microorganisms and hosts has been generated by interactive natural selection occurred between them. The symbiosis information that has been formed by interactive natural selection during a long evolutionary process must be recorded in DNA sequences. According to this point of view,we analyzed the phylogeny of 9 intestinal bacteria genera using their contents in intestines of 8 Cyrinidate species. At the same time,we fetched the 16S rRNA gene DNA sequences of 43 intestinal bacteria species being included in these nine genera of six intestinal families from GeneBank and constructed phylogenetic trees by NJ and MP methods. The NJ tree and MP tree have the same topo...
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The silkworm (Bombyx mori L.) is a lepidopteran insect with a long history of significant agricultural value. We have constructed the first amplified fragment length polymorphism (AFLP) genetic linkage map of the silkworm B. mori at a LOD... more
The silkworm (Bombyx mori L.) is a lepidopteran insect with a long history of significant agricultural value. We have constructed the first amplified fragment length polymorphism (AFLP) genetic linkage map of the silkworm B. mori at a LOD score of 2.5. The mapping AFLP markers were genotyped in 47 progeny from a backcross population of the cross no. 782 x od100. A total of 1248 (60.7%) polymorphic AFLP markers were detected with 35 PstI/TaqI primer combinations. Each of the primer combinations generated an average of 35.7 polymorphic AFLP markers. A total of 545 (44%) polymorphic markers are consistent with the expected segregation ratio of 1:1 at the significance level of P = 0.05. Of the 545 polymorphic markers, 356 were assigned to 30 linkage groups. The number of markers on linkage groups ranged from 4 to 36. There were 21 major linkage groups with 7-36 markers and 9 relatively small linkage groups with 4-6 markers. The 30 linkage groups varied in length from 37.4 to 691.0 cM. T...
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Prostasin, a serine protease, is suggested to be a novel mechanism regulating the epithelial sodium channel (ENaC) expressed in the distal nephron. This study aimed to evaluate whether the human prostasin gene is a novel candidate gene... more
Prostasin, a serine protease, is suggested to be a novel mechanism regulating the epithelial sodium channel (ENaC) expressed in the distal nephron. This study aimed to evaluate whether the human prostasin gene is a novel candidate gene underlying blood pressure (BP) elevation. In a sample of healthy African-American (AA) and European-American (EA) twin subjects aged 17.6 +/- 3.3 years (n = 920, 45% AAs), race-specific tagging single-nucleotide polymorphisms (tSNPs) were identified to tag all the available SNPs +/- 2 kb up- and downstream of the prostasin gene from HapMap at r2 of 0.8-1.0. Selection yielded four tSNPs in AAs and one in EAs, with one tSNP (rs12597511: C to T) present in both AAs and EAs. For rs12597511, CT and TT genotypes exhibited higher systolic BP (SBP) than CC genotype (115.9 +/- 1.1 mm Hg vs. 113.7 +/- 0.6 mm Hg, P = 0.025 (AAs); and 110.7 +/- 0.5 mm Hg vs. 109.6 +/- 0.6 mm Hg, P = 0.115 (EAs)). CT and TT genotypes compared with CC genotype showed a significant ...
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Background:Our research group recently reported that aorto-radial (radial) and aorto-dorsalis-pedis (foot) pulse wave velocity (PWV) as proxies of arterial stiffness are substantially heritable in healthy youth. This article aimed at... more
Background:Our research group recently reported that aorto-radial (radial) and aorto-dorsalis-pedis (foot) pulse wave velocity (PWV) as proxies of arterial stiffness are substantially heritable in healthy youth. This article aimed at uncovering the genetic contributions of adhesion molecules, key members in the inflammatory process, to PWV in these young individuals.Methods:Radial and foot PWV were noninvasively measured with applanation tonometry in 702 black and white subjects (42% blacks, mean age 17.7 ± 3.3 years) from the Georgia Cardio vascular Twin Study. Eight functional polymorphisms from genes for E-selectin (SELE), P-selectin (SELP), intercellular adhesion molecules-1 (ICAM1), and vascular cell adhesion molecules-1 (VCAM1) were genotyped.Results:Youth with Ser290Asn or Asn290Asn genotype (SELP) compared to those with Ser290Ser had an increase in both radial and foot PWV (6.61 ± 0.07 vs. 6.41 ± 0.05 m/s,p= .026; 7.22 ± 0.05 vs. 7.04 ± 0.04 m/s,p= .007). TT homozygotes of r...
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Identification of genes differentially expressed across multiple conditions has become an important statistical problem in analyzing large-scale microarray data. Many statistical methods have been developed to address the challenging... more
Identification of genes differentially expressed across multiple conditions has become an important statistical problem in analyzing large-scale microarray data. Many statistical methods have been developed to address the challenging problem. Therefore, an extensive comparison among these statistical methods is extremely important for experimental scientists to choose a valid method for their data analysis. In this study, we conducted simulation studies to compare six statistical methods: the Bonferroni (B-) procedure, the Benjamini and Hochberg (BH-) procedure, the Local false discovery rate (Localfdr) method, the Optimal Discovery Procedure (ODP), the Ranking Analysis of F-statistics (RAF), and the Significant Analysis of Microarray data (SAM) in identifying differentially expressed genes. We demonstrated that the strength of treatment effect, the sample size, proportion of differentially expressed genes and variance of gene expression will significantly affect the performance of ...
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Most studies of differential gene-expressions have been conducted between two given conditions. The two-condition experimental (TCE) approach is simple in that all genes detected display a common differential expression pattern responsive... more
Most studies of differential gene-expressions have been conducted between two given conditions. The two-condition experimental (TCE) approach is simple in that all genes detected display a common differential expression pattern responsive to a common two-condition difference. Therefore, the genes that are differentially expressed under the other conditions other than the given two conditions are undetectable with the TCE approach. In order to address the problem, we propose a new approach called multiple-condition experiment (MCE) without replication and develop corresponding statistical methods including inference of pairs of conditions for genes, new t-statistics, and a generalized multiple-testing method for any multiple-testing procedure via a control parameter C. We applied these statistical methods to analyze our real MCE data from breast cancer cell lines and found that 85 percent of gene-expression variations were caused by genotypic effects and genotype-ANAX1 overexpression...
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It is becoming clear that the etiology of complex diseases involves not only genetic and environmental factors but also gene-environment (GE) interactions. Therefore, it is important to take account of all these factors to improve the... more
It is becoming clear that the etiology of complex diseases involves not only genetic and environmental factors but also gene-environment (GE) interactions. Therefore, it is important to take account of all these factors to improve the power of an epidemiological study design. We propose here a novel parent-child pair (PCP) design for this purpose. In comparison with conventional designs, this approach has the following advantages: (a) PCP is a 4 x 16 design consisting of pairs of parent-child (PC) genotype statuses, PC exposure statuses and PC disease statuses. Therefore, it utilizes more information than the traditional approaches in association studies; (b) It can determine whether findings in studies of association between disease and genetic or environmental factors and their interaction are spurious, arising from Hardy-Weinberg disequilibrium or the other factors; (c) Since the information from both parents and children of the PC pairs are used in this design, it has high power for detecting association of candidate gene, exposure with a complex disease and GE interaction. We also present a set of estimates of relative risks of candidate genes, exposures and GE interactions under the multiplicative model and a method for computing the sample size requirements to test for these relative risks in the context of the PCP design.