• Genomics & Informatics
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• v.5 no.4
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• pp.143-151
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• 2007

To understand the mechanism of transcriptional regulation, it is essential to detect promoters and regulatory elements. Various kinds of methods have been introduced to improve the prediction accuracy of regulatory elements. Since there are few experimentally validated regulatory elements, previous studies have used criteria based solely on the level of scores over background sequences. However, selecting the detection criteria for different prediction methods is not feasible. Here, we studied the calibration of thresholds to improve regulatory element prediction. We predicted a regulatory element using MATCH, which is a powerful tool for transcription factor binding site (TFBS) detection. To increase the prediction accuracy, we used a regulatory potential (RP) score measuring the similarity of patterns in alignments to those in known regulatory regions. Next, we calibrated the thresholds to find relevant scores, increasing the true positives while decreasing possible false positives. By applying various thresholds, we compared predicted regulatory elements with validated regulatory elements from the Open Regulatory Annotation (ORegAnno) database. The predicted regulators by the selected threshold were validated through enrichment analysis of muscle-specific gene sets from the Tissue-Specific Transcripts and Genes (T-STAG) database. We found 14 known muscle-specific regulators with a less than a 5% false discovery rate (FDR) in a single TFBS analysis, as well as known transcription factor combinations in our combinatorial TFBS analysis.

• Genomics & Informatics
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• v.13 no.2
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• pp.53-59
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• 2015

In developing countries threat of cholera is a significant health concern whenever water purification and sewage disposal systems are inadequate. Vibrio cholerae is one of the responsible bacteria involved in cholera disease. The complete genome sequence of V. cholerae deciphers the presence of various genes and hypothetical proteins whose function are not yet understood. Hence analyzing and annotating the structure and function of hypothetical proteins is important for understanding the V. cholerae. V. cholerae O139 is the most common and pathogenic bacterial strain among various V. cholerae strains. In this study sequence of six hypothetical proteins of V. cholerae O139 has been annotated from NCBI. Various computational tools and databases have been used to determine domain family, protein-protein interaction, solubility of protein, ligand binding sites etc. The three dimensional structure of two proteins were modeled and their ligand binding sites were identified. We have found domains and families of only one protein. The analysis revealed that these proteins might have antibiotic resistance activity, DNA breaking-rejoining activity, integrase enzyme activity, restriction endonuclease, etc. Structural prediction of these proteins and detection of binding sites from this study would indicate a potential target aiding docking studies for therapeutic designing against cholera.

• Proceedings of the Korean Information Science Society Conference
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• 2003.10b
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• pp.742-744
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• 2003

PDB로부터 얻은 51개의 단백질-RNA 복합체를 대상으로 기존 연구에서 얻은 단백질과 RNA의 결합 성향성 값과 본 논문에서 새로 구한 단백질의 표면 노출정도에 따른 결합 성향성 값을 이용하여 단백질의 결합 기대치를 구한다. 또한 구한 결합 기대치를 활용하여 새로운 단백질-RNA 복합체를 대상으로 단백질의 결합 부위 예측을 시도하였다. 결합 기대치는 0.240 이상인 경우 결합할 가능성이 높은 것으로 판별하였고, 그 결과 단백질의 결합 후보지를 전체 단백질의 25% 정도로 줄일 수 있었다.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.156-161
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• 2007

Rapid advances in pharmacogenomic research have provided important information to improve drug selection, to maximize drug efficacy, and to minimize drug adverse reaction. The SNPs that are the most abundant type of genetic variants have been proven as valid biomarkers to give information on the prediction of pharmacokinetic/pharmacodynamic properties of drugs based on genotype. In order to elucidate a correlation between SNPs of calcium channel encoding gene and adverse reactions of calcium channel blockers, we investigated SNPs in CACNA1C gene known as a binding site of calcium channel blocker. 96 patients with hypertension who had taken or are taking an antihypertensive drug, 1,4-dihydropyridine (DHP) were included for analysis. These patients were composed of 47 patients with adverse drug reactions (ADR) such as edema from calcium channel blockers and 49 patients without ADR as a control group. The exons encoding the drug binding sites were amplified by PCR using specific primers, and SNPs were analyzed by direct sequencing. We found that there was no SNP in the exons encoding DHP binding site, but four novel SNPs in the exon-intron junction region. However, four novel SNPs were not associated with the ADR of calcium channel blockers. In conclusion, this study showed that ADR from calcium channel blockers may not be caused by SNPs of the binding sites of calcium channel blockers in CACNA1C gene.

• Journal of Integrative Natural Science
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• v.6 no.2
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• pp.100-103
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• 2013

Using computational approaches we can dock small molecules into the structures of Macromolecular targets and then score their potential complementarity to binding sites is widely used in hit identification and lead optimization techniques. This review seeks to provide the application of docking in structure-based drug design (binding mode prediction, Lead Identification and Lead optimization), and also discussed how to manage errors in docking methodology in order to overcome certain limitations of docking and scoring algorithm.

• BMB Reports
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• v.44 no.4
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• pp.250-255
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• 2011

In multicellular organisms, including humans, understanding expression specificity at the tissue level is essential for interpreting protein function, such as tissue differentiation. We developed a prediction approach via generated sequence features from overrepresented patterns in housekeeping (HK) and tissue-specific (TS) genes to classify TS expression in humans. Using TS domains and transcriptional factor binding sites (TFBSs), sequence characteristics were used as indices of expressed tissues in a Random Forest algorithm by scoring exclusive patterns considering the biological intuition; TFBSs regulate gene expression, and the domains reflect the functional specificity of a TS gene. Our proposed approach displayed better performance than previous attempts and was validated using computational and experimental methods.

• Microbiology and Biotechnology Letters
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• v.47 no.2
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• pp.278-288
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• 2019

In the present investigation, we attempted to design a protocol to develop a hybrid protein with better bioremediation capacity. Using in silico approaches, a Hybrid Open Reading Frame (Hybrid ORF) is developed targeting the genes of microorganisms known for degradation of organophosphates. Out of 21 genes identified through BLAST search, 8 structurally similar genes (opdA, opd, opaA, pte RO, pdeA, parC, mpd and phnE) involved in biodegradation were screened. Gene conservational analysis categorizes these organophosphates degrading 8 genes into 4 super families i.e., Metallo-dependent hydrolases, Lactamase B, MPP and TM_PBP2 superfamily. Hybrid protein structure was modeled using multi-template homology modeling (3S07_A; 99%, 1P9E_A; 98%, 2ZO9_B; 33%, 2DXL_A; 33%) by $Schr{\ddot{o}}dinger$ software suit version 10.4.018. Structural verification of protein models was done using Ramachandran plot, it was showing 96.0% residue in the favored region, which was verified using RAMPAGE. The phosphotriesterase protein was showing the highest structural similarity with hybrid protein having raw score 984. The 5 binding sites of hybrid protein were identified through binding site prediction. The docking study shows that hybrid protein potentially interacts with 10 different organophosphates. The study results indicate that the hybrid protein designed has the capability of degrading a wide range of organophosphate compounds.

• Proceedings of the Korean Information Science Society Conference
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• 2005.11a
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• pp.967-969
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• 2005

유전자의 발현은 전사인자와 전사인자 결합부위의 결함에 의해 조절된다. 따라서 이러한 결합부위를 예측하는 것은 유전학 분야에서 중요한 이슈이다. 본 논문에서는 접미사 배열을 이용하여 전사인자가 결합할 것으로 예상되는 DNA 서열들의 공통서열을 추출하고, 이를 다시 입력 서열과 부분 정렬을 수행함으로써 전사인자가 결합하는 부위를 예측하는 알고리즘을 제시한다. 그리고 알려진 전사인자 결합부위를 가진 데이터로 실험한 결과를 통해 제시된 추출 방법의 성능에 대하여 논의한다.

• Proceedings of the Korean Information Science Society Conference
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• 2003.10b
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• pp.820-822
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• 2003

접미사 배열이나 접미사 트리는 대용량의 서열데이터를 효율적으로 검색, 저장할 수 있는 인덱스 자료구조로서 바이오인포매틱스와 같이 대용량 데이터의 처리. 분석이 필요한 분야에 이용될 수 있다. 최근 들어 접미사 배열에 대한 연구가 활발히 진행되어 접미사 배열의 효율적인 저장, 선형시간 생성 및 선형시간 탐색 알고리즘들이 개발되었다. 본 논문에서는 같은 전사인자가 결합할 것으로 예상되는 여러 개의 전사조절부위에 대한 DNA 서열들이 입력으로 주어졌을 때 전사인자가 결합하는 부위를 예측하는 방법을 제시한다. 이를 위해 최근에 제시된 선형시간 접미사 배열 생성 알고리즘을 이용하고 TRANSFAC과 EMBL 등의 DB를 이용하여 실험을 통해 본 논문에서 제시하는 방법의 정확도를 평가한다.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.3
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• pp.309-315
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• 2018

Objective: This study aimed to test the expression patterns of ERBB receptor feedback inhibitor 1 (ERRFI1) before and after exercise and the association of non-synonymous single-nucleotide polymorphisms (nsSNPs) of horse ERRFI1 with racing traits in Thoroughbreds. Methods: We performed bioinformatics and gene expression analyses for horse ERRFI1. Transcription factor (TF) binding sites in the 5'-regulatory region of this gene were identified through a tool for prediction of TF-binding site (PROMO). A general linear model was used to detect the association between the nsSNP (LOC42830758 A to G) and race performance. Results: Quantitative polymerase chain reaction analysis showed that expression level of ERRFI1 after exercise was 1.6 times higher than that before exercise. Ten transcription factors were predicted from the ERRFI1 regulatory region. A novel nsSNP (LOC42830758 A to G) was found in ERRFI1, which was associated with three racing traits including average prize money, average racing index, and 3-year-old starts percentile ranking. Conclusion: Our analysis will be helpful as a basis for studying genes and SNPs that affect race performance in racehorses.