المؤلفون: Liu, Chun-Chi, Lin, Chin-Chung, Li, Ker-Chau, Chen, Wen-Shyen E, Chen, Jiun-Ching, Yang, Ming-Te, Yang, Pan-Chyr, Chang, Pei-Chun, Chen, Jeremy JW

الوصف: Background Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos. Results We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes. Conclusion The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides ...

العلاقة: http://www.biomedcentral.com/1471-2105/8/164Test

الإتاحة: http://www.biomedcentral.com/1471-2105/8/164Test

المؤلفون: Yu, Tianwei, Li, Ker-Chau

مصطلحات موضوعية: SYSTEMS BIOLOGY

الوصف: Motivation: Microarray gene expression and cross-linking chromatin immunoprecipitation data contain voluminous information that can help the identification of transcriptional regulatory networks at the full genome scale. Such high-throughput data are noisy however. In contrast, from the biomedical literature, we can find many evidenced transcription factor (TF)–target gene binding relationships that have been elucidated at the molecular level. But such sporadically generated knowledge only offers glimpses on limited patches of the network. How to incorporate this valuable knowledge resource to build more reliable network models remains a question. Results: We present a modified factor analysis approach. Our algorithm starts with the evidenced TF–gene linkages. It iterates between the network configuration estimation step and the connection strength estimation step, using the high-throughput data, till convergence. We report two comprehensive regulatory networks obtained for Saccharomyces cerevisiae , one under the normal growth condition and the other under the environmental stress condition. Contact: kcli@stat.ucla.edu Supplementary information: http://kiefer.stat.ucla.edu/lap2/download/bti656_supplement.pdfTest

وصف الملف: text/html

العلاقة: http://bioinformatics.oxfordjournals.org/cgi/content/short/21/21/4033Test; http://dx.doi.org/10.1093/bioinformatics/bti656Test

الإتاحة: https://doi.org/10.1093/bioinformatics/bti656Test
http://bioinformatics.oxfordjournals.org/cgi/content/short/21/21/4033Test

المؤلفون: Yu, Tianwei, Sun, Wei, Yuan, Shinsheng, Li, Ker-Chau

مصطلحات موضوعية: SYSTEMS BIOLOGY

الوصف: Motivation: Cellular processes are not isolated groups of events. Nevertheless, in most microarray analyses, they tend to be treated as standalone units. To shed light on how various parts of the interlocked biological processes are coordinated at the transcription level, there is a need to study the between-unit expressional relationship directly. Results: We approach this issue by constructing an index of correlation function to convey the global pattern of coexpression between genes from one process and genes from the entire genome. Processes with similar signatures are then identified and projected to a process-to-process association graph. This top–down method allows for detailed gene-level analysis between linked processes to follow up. Using the cell-cycle gene-expression profiles for Saccharomyces cerevisiae , we report well-organized networks of biological processes that would be difficult to find otherwise. Using another dataset, we report a sharply different network structure featuring cellular responses under environmental stress. Contact: kcli@stat.ucla.edu Supplementary information: http://kiefer.stat.ucla.edu/lap2/download/KL_supplement.pdfTest

وصف الملف: text/html

العلاقة: http://bioinformatics.oxfordjournals.org/cgi/content/short/21/18/3651Test; http://dx.doi.org/10.1093/bioinformatics/bti599Test

الإتاحة: https://doi.org/10.1093/bioinformatics/bti599Test
http://bioinformatics.oxfordjournals.org/cgi/content/short/21/18/3651Test

المؤلفون: Su, Sheng-Fang, Liu, Chia-Hsin, Cheng, Chiou-Ling, Ho, Chao-Chi, Yang, Tsung-Ying, Chen, Kun-Chieh, Hsu, Kuo-Hsuan, Tseng, Jeng-Sen, Chen, Huei-Wen, Chang, Gee-Chen, Yu, Sung-Liang, Li, Ker-Chau

المصدر: JCO Precision Oncology; 5/10/2021, Vol. 5, p418-431, 14p

مصطلحات موضوعية: DNA methylation, EPIGENOMICS, EPIDERMAL growth factor receptors, METHYLATION, KINASE inhibitors

مستخلص: PURPOSE: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) show efficacy in treating patients with lung adenocarcinoma with EGFR -activating mutations. However, a significant subset of targeted patients fail to respond. Unlike acquired resistance (AR), intrinsic resistance (IR) remains poorly understood. We investigated whether epigenomic factors contribute to patient-to-patient heterogeneity in the EGFR-TKI response and aimed to characterize the IR subpopulation that obtains no benefit from EGFR-TKIs. PATIENTS AND METHODS: We conducted genome-wide DNA methylation profiling of 79 tumors sampled from patients with advanced lung adenocarcinoma before they received EGFR-TKI treatment and analyzed the patient responses. Pyrosequencing was performed in a validation cohort of 163 patients with EGFR -activating mutations. RESULTS: A DNA methylation landscape of 216 CpG sites with differential methylation was established to elucidate the association of DNA methylation with the characteristics and EGFR-TKI response status of the patients. Functional analysis of 37 transcription-repressive sites identified the enrichment of transcription factors, notably homeobox (HOX) genes. DNA methylation of HOXB9 (cg13643585) in the enhancer region yielded 88% sensitivity for predicting drug response (odds ratio [OR], 6.64; 95% CI, 1.98 to 25.23; P =.0009). Pyrosequencing validated that HOXB9 gained methylation in patients with a poor EGFR-TKI response (OR, 3.06; 95% CI, 1.13 to 8.19; P =.019). CONCLUSION: Our data suggest that homeobox DNA methylation could be a novel tumor cellular state that can aid the precise categorization of tumor heterogeneity in the study of IR to EGFR-TKIs. We identified, for the first time, an epigenomic factor that can potentially complement DNA mutation status in discriminating patients with lung adenocarcinoma who are less likely to benefit from EGFR-TKI treatment, thereby leading to improved patient management in precision medicine. [ABSTRACT FROM AUTHOR]

: Copyright of JCO Precision Oncology is the property of American Society of Clinical Oncology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Wu, Ming-Fang, Lin, Chih-An, Yuan, Tzu-Hang, Yeh, Hsiang-Yuan, Su, Sheng-Fang, Guo, Chin-Lin, Chang, Gee-Chen, Li, Ker-Chau, Ho, Chao-Chi, Chen, Huei-Wen

المصدر: Cancer Immunology, Immunotherapy; May2021, Vol. 70 Issue 5, p1435-1450, 16p

مصطلحات موضوعية: LUNG cancer, CANCER patients, PLEURAL effusions, PROGRAMMED death-ligand 1, LUNGS, MACROPHAGES

مستخلص: Background: Malignant pleural effusion (MPE)-macrophage (Mφ) of lung cancer patients within unique M1/M2 spectrum showed plasticity in M1–M2 transition. The M1/M2 features of MPE-Mφ and their significance to patient outcomes need to be clarified; furthermore, whether M1-repolarization could benefit treatment remains unclear. Methods: Total 147 stage-IV lung adenocarcinoma patients undergoing MPE drainage were enrolled for profiling and validation of their M1/M2 spectrum. In addition, the MPE-Mφ signature on overall patient survival was analyzed. The impact of the M1-polarization strategy of patient-derived MPE-Mφ on anti-cancer activity was examined. Results: We found that MPE-Mφ expressed both traditional M1 (HLA-DRA) and M2 (CD163) markers and showed a wide range of M1/M2 spectrum. Most of the MPE-Mφ displayed diverse PD-L1 expression patterns, while the low PD-L1 expression group was correlated with higher levels of IL-10. Among these markers, we identified a novel two-gene MPE-Mφ signature, IL-1β and TGF-β1, representing the M1/M2 tendency, which showed a strong predictive power in patient outcomes in our MPE-Mφ patient cohort (N = 60, p = 0.013) and The Cancer Genome Atlas Lung Adenocarcinoma dataset (N = 478, p < 0.0001). Significantly, β-glucan worked synergistically with IFN-γ to reverse the risk signature by repolarizing the MPE-Mφ toward the M1 pattern, enhancing anti-cancer activity. Conclusions: We identified MPE-Mφ on the M1/M2 spectrum and plasticity and described a two-gene M1/M2 signature that could predict the outcome of late-stage lung cancer patients. In addition, we found that "re-education" of these MPE-Mφ toward anti-cancer M1 macrophages using clinically applicable strategies may overcome tumor immune escape and benefit anti-cancer therapies. [ABSTRACT FROM AUTHOR]

: Copyright of Cancer Immunology, Immunotherapy is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Cheng, Ching-Shui, Li, Ker-Chau

المصدر: Statistica Sinica, 1995 Jul 01. 5(2), 617-639.

الوصول الحر: https://www.jstor.org/stable/24305061Test

المؤلفون: Carroll, R. J., Li, Ker-Chau

المصدر: Statistica Sinica, 1995 Jul 01. 5(2), 667-688.

الوصول الحر: https://www.jstor.org/stable/24305063Test

المؤلفون: Duan, Naihua, Li, Ker-Chau

المصدر: Statistica Sinica, 1991 Jan 01. 1(1), 127-136.

الوصول الحر: https://www.jstor.org/stable/24303996Test

المؤلفون: Chen, Hsuan-Yu, Yu, Sung-Liang, Ho, Bing-Ching, Su, Kang-Yi, Hsu, Yi-Chiung, Chang, Chi-Sheng, Li, Yu-Cheng, Yang, Shi-Yi, Hsu, Pin-Yen, Ho, Hao, Chang, Ya-Hsuan, Chen, Chih-Yi, Yang, Hwai-I, Hsu, Chung-Ping, Yang, Tsung-Ying, Chen, Kun-Chieh, Hsu, Kuo-Hsuan, Tseng, Jeng-Sen, Hsia, Jiun-Yi, Chuang, Cheng-Yen, Yuan, Shinsheng, Lee, Mei-Hsuan, Liu, Chia-Hsin, Wu, Guan-I, Hsiung, Chao A., Chen, Yuh-Min, Wang, Chih-Liang, Huang, Ming-Shyan, Yu, Chong-Jen, Chen, Kuan-Yu, Tsai, Ying-Huang, Su, Wu-Chou, Chen, Huei-Wen, Chen, Jeremy J. W., Chen, Chien-Jen, Chang, Gee-Chen, Yang, Pan-Chyr, Li, Ker-Chau

المساهمون: National Cheng Kung University

الوصف: PurposeAdenocarcinoma is the most dominant type of lung cancer in never-smoker patients. The risk alleles from genome-wide association studies have small odds ratios and unclear biologic roles. Here we have taken an approach featuring suitable medical actionability to identify alleles with low population frequency but high disease-causing potential.Patients and MethodsWhole-genome sequencing was performed for a family with an unusually high density of lung adenocarcinoma with available DNA from the affected mother, four affected daughters, and one nonaffected son. Candidate risk alleles were confirmed by matrix-assisted laser desorption ionization time of flight mass spectroscopy. Validation was conducted in an external cohort of 1,135 participants without cancer and 1,312 patients with lung adenocarcinoma. Family follow-ups were performed by genotyping the relatives of the original proband and the relatives of the identified risk-allele carriers. Low-dose computed tomography scans of the chest were evaluated for lung abnormalities.ResultsYAP1 R331W missense mutation from the original family was identified and validated in the external controls and the cohort with lung adenocarcinoma. The YAP1 mutant-allele carrier frequency was 1.1% in patients with lung adenocarcinoma compared with 0.18% in controls (P = .0095), yielding an odds ratio (adjusted for age, sex, and smoking status) of 5.9. Among the relatives, YAP1-mutant carriers have overwhelmingly higher frequencies of developing lung adenocarcinoma or ground-glass opacity lung lesions than those who do not carry the mutation (10:0 v 1:7; P < .001). YAP1 mutation was shown to increase the colony formation ability and invasion potential of lung cancer cells.ConclusionThese results implicated YAP1 R331W as an allele predisposed for lung adenocarcinoma with high familial penetrance. Low-dose computed tomography scans may be recommended to this subpopulation, which is at high risk for lung cancer, for personalized prevention and health management.

وصف الملف: 106 bytes; text/html

العلاقة: JOURNAL OF CLINICAL ONCOLOGY, Vol. 33, No. 20, pp. 2303-U128; http://ir.lib.ncku.edu.tw/handle/987654321/167388Test; http://ir.lib.ncku.edu.tw/bitstream/987654321/167388/1/index.htmlTest

الإتاحة: https://doi.org/10.1200/JCO.2014.59.3590Test
http://ir.lib.ncku.edu.tw/handle/987654321/167388Test
http://ir.lib.ncku.edu.tw/bitstream/987654321/167388/1/index.htmlTest

المؤلفون: Chen, Jie‐Fu, Ho, Hao, Lichterman, Jake, Lu, Yi‐Tsung, Zhang, Yang, Garcia, Mitch A., Chen, Shang‐Fu, Liang, An‐Jou, Hodara, Elisabeth, Zhau, Haiyen E., Hou, Shuang, Ahmed, Rafi S., Luthringer, Daniel J., Huang, Jiaoti, Li, Ker‐Chau, Chung, Leland W. K., Ke, Zunfu, Tseng, Hsian‐Rong, Posadas, Edwin M.

المساهمون: National Institutes of Health, U.S. Department of Defense, Prostate Cancer Foundation, National Natural Science Foundation of China

المصدر: Cancer ; volume 121, issue 18, page 3240-3251 ; ISSN 0008-543X 1097-0142

الوصف: BACKGROUND Although enumeration of circulating tumor cells (CTCs) has shown some clinical value, the pool of CTCs contains a mixture of cells that contains additional information that can be extracted. The authors subclassified CTCs by shape features focusing on nuclear size and related this with clinical information. METHODS A total of 148 blood samples were obtained from 57 patients with prostate cancer across the spectrum of metastatic states: no metastasis, nonvisceral metastasis, and visceral metastasis. CTCs captured and enumerated on NanoVelcro Chips (CytoLumina, Los Angeles, Calif) were subjected to pathologic review including nuclear size. The distribution of nuclear size was analyzed using a Gaussian mixture model. Correlations were made between CTC subpopulations and metastatic status. RESULTS Statistical modeling of nuclear size distribution revealed 3 distinct subpopulations: large nuclear CTCs, small nuclear CTCs, and very small nuclear CTCs (vsnCTCs). Small nuclear CTCs and vsnCTC identified those patients with metastatic disease. However, vsnCTC counts alone were found to be elevated in patients with visceral metastases when compared with those without (0.36 ± 0.69 vs 1.95 ± 3.77 cells/mL blood; P <.001). Serial enumeration studies suggested the emergence of vsnCTCs occurred before the detection of visceral metastases. CONCLUSIONS There are morphologic subsets of CTCs that can be identified by fundamental pathologic approaches, such as nuclear size measurement. The results of this observational study strongly suggest that CTCs contain relevant information regarding disease status. In particular, the detection of vsnCTCs was found to be correlated with the presence of visceral metastases and should be formally explored as a putative blood‐borne biomarker to identify patients at risk of developing this clinical evolution of prostate cancer. Cancer 2015;121:3240–3251. © 2015 American Cancer Society .

الإتاحة: https://doi.org/10.1002/cncr.29455Test