Biomedical subjects

Hongshik Ahn

Publications and source records attributed to Hongshik Ahn.

5 recordsLinked to original sources

PubMed2005

An age-adjusted bootstrap-based Poly-k test.

The assumption of an asymptotic normal distribution of some test statistics may be invalid in certain dose-response trend tests. For instance, the survival-adjusted Cochran-Armitage test, known as the Poly-k test, is asymptotically standard normal under the null hypothesis. However, the asymptotic normality is not valid if there is a deviation from the tumour onset distribution that is assumed in this test or if the competing risks survival rates differ across groups. We develop an age-adjusted bootstrap-based method to assess the significance of assumed asymptotic normal tests for animal carcinogenicity data. The proposed method differs from conventional bootstrap methods in the aspect of preserving the mortality rate in each dose group under the null hypothesis of equal tumour incidence rates among the groups. We investigate an empirical distribution of the Poly-3 (P3) trend test statistic using the proposed age-adjusted bootstrap-based method and compare it with the P3 test statistic referenced to the assumed standard normal distribution. A simulation study is conducted to evaluate the robustness of these tests to various Weibull-family tumour onset distributions. The proposed method is applied to National Toxicology Program data sets to evaluate a dose-related trend of a test substance on the incidence of neoplasms.

Age Factors↗

PubMed2004

Statistical approaches in the analysis of gene expression data derived from bone regeneration specific cDNA microarrays.

Recent advances in molecular biology (e.g., cDNA microarray technology) enables the simultaneous monitoring of the expression level of thousands of genes. Due to the massive amount of complex data generated, sophisticated statistical approaches are necessary in order to properly address the experimental investigation. In this paper, we present statistical analysis of cDNA microarray data derived from bone regeneration experiments. Several interesting features from these data distinguish it from commonly used microarray experiment (i.e., separate hybridization of mRNA samples from reference and experimental tissues, selectively spotted cDNA sequences and 1060 systematically selected blank spots included in each array). Using this data set, we propose new methods for bioinformatic data normalization, as well as the modification and application of various other published methods in order to identify co-regulated gene expression patterns during the healing of a bone fracture. The proposed normalization methods perform effectively to eliminate the variations with a simple algorithm. Results from our cluster analysis revealed several clusters having distinct gene expression patterns during fracture healing. Our simulation study supports the reliability of the proposed methods.

Adenosylmethionine Decarboxylase↗

PubMed2003

Estimation of k for the poly-k test with application to animal carcinogenicity studies.

This paper extends the survival-adjusted Cochran-Armitage test in order to achieve improved robustness to a variety of tumour onset distributions. The Cochran-Armitage test is routinely applied for detecting a linear trend in the incidence of a tumour of interest across dose groups. To improve the robustness to the effects of differential mortality across groups, Bailer and Portier introduced the poly-3 test by a survival adjustment using a fractional weighting scheme for subjects not at full risk of tumour development. The performance of the poly-3 test depends on how closely it represents the correct specification of the time-at-risk weight in the data. Bailer and Portier further suggested that this test can be improved by using a general k reflecting the shape of the tumour onset distribution. In this paper, we propose a method to estimate k by equating the empirical lifetime tumour incidence rate obtained from the data based on the fractional weighting scheme to a separately estimated cumulative lifetime tumour incidence rate. This poly-k test with the statistically estimated k appears to perform better than the poly-3 test which is conducted without prior knowledge of the tumour onset distribution. Our simulation shows that the proposed method improves the robustness to various tumour onset distributions in addition to the robustness to the effects of mortality achieved by the poly-3 test. Large sample properties are shown via simulations to illustrate the consistency of the proposed method. The proposed methods are applied to analyse two real data sets. One is to find a dose-related linear trend on animal carcinogenicity, and the other is to test an effect of calorie restriction on experimental animals.

2-Acetylaminofluorene↗

PubMed2002

Transcriptional profiling of bone regeneration. Insight into the molecular complexity of wound repair.

The healing of skeletal fractures is essentially a replay of bone development, involving the closely regulated, interdependent processes of chondrogenesis and osteogenesis. Using a rat femur model of bone healing to determine the degree of transcriptional complexity of these processes, suppressive subtractive hybridization (SSH) was performed between RNA isolated from intact bone to that of callus from post-fracture (PF) days 3, 5, 7, and 10 as a means of identifying up-regulated genes in the regenerative process. Analysis of 3,635 cDNA clones revealed 588 known genes (65.8%, 2392 clones) and 821 expressed sequence tags (ESTs) (31%, 1,127). The remaining 116 cDNAs (3.2%) yielded no homology and presumably represent novel genes. Microarrays were then constructed to confirm induction of expression and determine the temporal profile of all isolated cDNAs during fracture healing. These experiments confirmed that approximately 90 and approximately 80% of the subtracted known genes and ESTs are up-regulated (> or = 2.5-fold) during the repair process, respectively. Clustering analysis revealed subsets of genes, both known and unknown, that exhibited distinct expression patterns over 21 days (PF), indicating distinct roles in the healing process. Additionally, this transcriptional profiling of bone repair revealed a host of activated signaling molecules and even pathways (i.e. Wnt). In summary, the data demonstrate, for the fist time, that the healing process is exceedingly complex, involves thousands of activated genes, and indicates that groups of genes rather than individual molecules should be considered if the regeneration of bone is to be accelerated exogenously.

Animals↗

PubMed2002

Age-adjusted exact trend tests in the event of rare occurrences.

Preclinical animal carcinogenicity studies are usually concerned with testing the statistical significance of a dose-response relationship. When the response consists of a rare event such as the development of a certain type of tumor, exact statistical methods are often employed. The exact randomization trend test based on the multivariate hypergeometric distribution is less powerful in the presence of treatment-related risks other than the specified response. Particularly, the loss of power becomes more pronounced when competing risks cause progressively higher mortality rates with increasing dose, which is usual in practice. An age-adjusted form of the randomization test is proposed to adjust for this effect. Permutational distribution for Peto's cause-of-death (COD) test is also explored and compared with its asymptotic counterpart by simulation. The use of COD information has been a controversial issue due to the subjectivity in the pathologists' determinations as well as for economic reasons. The proposed age-adjusted exact test does not require COD, and it is shown to compare favorably to the COD tests via an extensive Monte Carlo simulation. Applications of the methods to two real data sets are included.

Age Factors↗