• Genomics & Informatics
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• v.18 no.4
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• pp.42.1-42.9
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• 2020

Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-Seq) is a powerful technology to profile the location of proteins of interest on a whole-genome scale. To identify the enrichment location of proteins, many programs and algorithms have been proposed. However, none of the commonly used peak calling programs could accurately explain the binding features of target proteins detected by ChIP-Seq. Here, publicly available data on 12 histone modifications, including H3K4ac/me1/me2/me3, H3K9ac/me3, H3K27ac/me3, H3K36me3, H3K56ac, and H3K79me1/me2, generated from a human embryonic stem cell line (H1), were profiled with five peak callers (CisGenome, MACS1, MACS2, PeakSeq, and SISSRs). The performance of the peak calling programs was compared in terms of reproducibility between replicates, examination of enriched regions to variable sequencing depths, the specificity-to-noise signal, and sensitivity of peak prediction. There were no major differences among peak callers when analyzing point source histone modifications. The peak calling results from histone modifications with low fidelity, such as H3K4ac, H3K56ac, and H3K79me1/me2, showed low performance in all parameters, which indicates that their peak positions might not be located accurately. Our comparative results could provide a helpful guide to choose a suitable peak calling program for specific histone modifications.

• KSII Transactions on Internet and Information Systems (TIIS)
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• v.13 no.4
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• pp.1765-1794
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• 2019

Genetic Programming (GP) is an intelligence technique whereby computer programs are encoded as a set of genes which are evolved utilizing a Genetic Algorithm (GA). In other words, the GP employs novel optimization techniques to modify computer programs; imitating the way humans develop programs by progressively re-writing them for solving problems automatically. Trial programs are frequently altered in the search for obtaining superior solutions due to the base is GA. These are evolutionary search techniques inspired by biological evolution such as mutation, reproduction, natural selection, recombination, and survival of the fittest. The power of GAs is being represented by an advancing range of applications; vector processing, quantum computing, VLSI circuit layout, and so on. But one of the most significant uses of GAs is the automatic generation of programs. Technically, the GP solves problems automatically without having to tell the computer specifically how to process it. To meet this requirement, the GP utilizes GAs to a "population" of trial programs, traditionally encoded in memory as tree-structures. Trial programs are estimated using a "fitness function" and the suited solutions picked for re-evaluation and modification such that this sequence is replicated until a "correct" program is generated. GP has represented its power by modifying a simple program for categorizing news stories, executing optical character recognition, medical signal filters, and for target identification, etc. This paper reviews existing literature regarding the GPs and their applications in different scientific fields and aims to provide an easy understanding of various types of GPs for beginners.

• Biomedical Science Letters
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• v.28 no.2
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• pp.109-119
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• 2022

Histone proteins can be modified by the addition of acetyl group or methyl group to specific amino acids. The modifications have different distribution patterns in chromatin. Recently, histone modifications are studied based on ChIP-seq data, which requires reasonable analysis of sequencing data depending on their distribution patterns. Here we have analyzed histone H3K27ac and H3K27me3 ChIP-seq data and it showed that the H3K27ac is enriched at narrow regions while H3K27me3 distributes broadly. To properly analyze the ChIP-seq data, we called peaks for H3K27ac and H3K27me3 using MACS2 (narrow option and broad option) and SICER methods, and compared propriety of the peaks using signal-to-background ratio. As results, H3K27ac-enriched regions were well identified by both methods while H3K27me3 peaks were properly identified by SICER, which indicates that peak calling method is more critical for histone modifications distributed broadly. When ChIP-seq data were compared in different sequencing depth (15, 30, 60, 120 M), high sequencing depth caused high false-positive rate in H3K27ac peak calling, but it reflected more properly the broad distribution pattern of H3K27me3. These results suggest that sequencing depth affects peak calling from ChIP-seq data and high sequencing depth is required for H3K27me3. Taken together, peak calling tool and sequencing depth should be chosen depending on the distribution pattern of histone modification in ChIP-seq analysis.

• Molecules and Cells
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• v.46 no.12
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• pp.764-777
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• 2023

Recombinant immunotoxins (RITs) are fusion proteins consisting of a targeting domain linked to a toxin, offering a highly specific therapeutic strategy for cancer treatment. In this study, we engineered and characterized RITs aimed at mesothelin, a cell surface glycoprotein overexpressed in various malignancies. Through an extensive screening of a large nanobody library, four mesothelin-specific nanobodies were selected and genetically fused to a truncated Pseudomonas exotoxin (PE24B). Various optimizations, including the incorporation of furin cleavage sites, maltose-binding protein tags, and tobacco etch virus protease cleavage sites, were implemented to improve protein expression, solubility, and purification. The RITs were successfully overexpressed in Escherichia coli, achieving high solubility and purity post-purification. In vitro cytotoxicity assays on gastric carcinoma cell lines NCI-N87 and AGS revealed that Meso(Nb2)-PE24B demonstrated the highest cytotoxic efficacy, warranting further characterization. This RIT also displayed selective binding to human and monkey mesothelins but not to mouse mesothelin. The competitive binding assays between different RIT constructs revealed significant alterations in IC₅₀ values, emphasizing the importance of nanobody specificity. Finally, a modification in the endoplasmic reticulum retention signal at the C-terminus further augmented its cytotoxic activity. Our findings offer valuable insights into the design and optimization of RITs, showcasing the potential of Meso(Nb2)-PE24B as a promising therapeutic candidate for targeted cancer treatment.

• Journal of Microbiology and Biotechnology
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• v.34 no.6
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• pp.1222-1228
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• 2024

Protein-specific antibodies are essential for various aspects of protein research, including detection, purification, and characterization. When specific antibodies are unavailable, protein tagging is a useful alternative. Small epitope tags, typically less than 10 amino acids, are widely used in protein research due to the simple modification through PCR and reduced impact on the target protein's function compared to larger tags. The 2B8 epitope tag (RDPLPFFPP), reported by us in a previous study, has high specificity and sensitivity to the corresponding antibody. However, when attached to the C-terminus of the target protein in immunoprecipitation experiments, we observed a decrease in detection signal with reduced immunity and low protein recovery. This phenomenon was not unique to 2B8 and was also observed with the commercially available Myc tag. Our study revealed that C-terminal tagging of small epitope tags requires the addition of more than one extra amino acid to enhance (restore) antibody immunities. Moreover, among the amino acids we tested, serine was the best for the 2B8 tag. Our findings demonstrated that the interaction between a small epitope and a corresponding paratope of an antibody requires an extra amino acid at the C-terminus of the epitope. This result is important for researchers planning studies on target proteins using small epitope tags.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1707-1714
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• 2012

Grb2 is an adapter protein involved in the signal transduction and cell communication. The Grb2 is responsible for initiation of kinase signaling by Ras activation which leads to the modification in transcription. Ligand based pharmacophore approach was applied to built the suitable pharmacophore model for Grb2. The best pharmacophore model was selected based on the statistical values and then validated by Fischer's randomization method and test set. Hypo1 was selected as a best pharmacophore model based on its statistical values like high cost difference (182.22), lowest RMSD (1.273), and total cost (80.68). It contains four chemical features, one hydrogen bond acceptor (HBA), two hydrophobic (HY), and one ring aromatic (RA). Fischer's randomization results also shows that Hypo1 have a 95% significant level. The correlation coefficient of test set was 0.97 which was close to the training set value (0.94). Thus Hypo1 was used for virtual screening to find the potent inhibitors from various chemical databases. The screened compounds were filtered by Lipinski's rule of five, ADMET and subjected to molecular docking studies. Totally, 11 compounds were selected as a best potent leads from docking studies based on the consensus scoring function and critical interactions with the amino acids in Grb2 active site.

• Journal of Broadcast Engineering
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• v.3 no.1
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• pp.69-84
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• 1998

In digital broadcasting, services such as digital satellite TV, cable TV and digital terrestrial TV, several video programs are compressed by MPEG-2, and then simultaneously transmitted over a conventional CBR (Constant Bit Rate) broadcasting channel. In this paper, we propose a joint quality control scheme to be able to accurately control the relative picture quality among the video programs, which is achieved by simdt;,nL'Ously controlling the video encoders to generate the VBR (Variable Bit Rate) compressed video streams. Our quality control scheme can prevent the video buffer overflow and underflow by total target bit allocation process, and also exactly control the relative picture quality in terms of PSNR (Peak Signal to Noise Ratio) between some programs requiring higher picture quality and others by rate-distortion modification. Furthermore we present a rate-distortion estimation method for MPEG-2 video, which is base of our joint quality control, and verify its performance by experiments. The most attractive features of this estimation method are as follows: 1) computational complexity is low because main operation for the estimation is to calculate the histogram of OCT coefficients into quantizer; 2) estimation results are very accurate enough to be applied to the practical MPEG-2 video coding applications. Simulation results show that the proposed joint quality control scheme accurately controls the relative picture quality among the video progran1s transmitted over a single channel as well as provides more consistent and higher picture quality than independent coding scheme that encodes each program independently.

• Journal of Digital Contents Society
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• v.16 no.2
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• pp.291-298
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• 2015

In a fast-paced information technology environment, consumption of video content is changing from one-way television viewing to VOD (Video on Demand) playing anywhere, anytime, on any device. This video-watching trend gives additional importance to videos with fine-speed-control, in addition to the strength of the digital video signal. Currently, many video players provide a fine-speed-control function which can speed up the video to skip a boring part, or slow it down to focus on an exciting scene. The audio information is just as important as the visual information for understanding the content of the speed-controlled video. Thus, a number of algorithms for fine-speed-control video-playing technologies have been proposed to solve the pitch distortion in the audio-processing area. In this study, well-known techniques for prosodic modification of speech signals, WSOLA (Waveform-Similarity-Based Overlap-Add), have been applied to analyze users' needs for fine-speed-control video playing. By surveying the users' preferred speeds on categorized video content and analyzing the results, this paper proposes that various fine-speed adjustments are needed to accommodate users' preferred video consumption.

• Journal of the Institute of Electronics Engineers of Korea TC
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• v.46 no.5
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• pp.95-103
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• 2009

An efficient symbol time synchronization scheme for IEEE 802.11n MIMO-OFDM based WLAN systems using cyclic shift diversity (CSD) preamble is proposed. CSD is used to prevent unintentional beamforming when the same preamble signal is transmitted through transmit antennas. However, it is difficult to find a proper starting-point of the OFDM symbol with the conventional algorithms because of time offset by multi-peaks which are result from cross-correlation of received CSD preamble with a known short training symbol. In addition, the performance of symbol time sync. is affected by AGC and packet detection position. In this paper, an optimal symbol time synch. algorithm which is composed of the boundary detection scheme between LTS and OFDM symbols, the verification scheme for enhancement of boundary detection accuracy, and the SNR-varying threshold estimation scheme is proposed. Simulation result show that the proposed algorithm has performance gains of 4.3dB in SNR compared to the conventional algorithms at the rate of 1% sync. failure probability for $2{\times}2$ MIMO-OFDM system and 18dB at 0.1% when maximum frequency offset exists. It also can be applied to $4{\times}4$ MIMO-OFDM system without any modification. Hence, it is very suitable for MIMO-OFDM WLAN systems using CSD preamble.

• Journal of the Institute of Electronics Engineers of Korea SD
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• v.45 no.5
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• pp.1-11
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• 2008

This work proposes a 15b 50MS/s CMOS pipeline ADC based on digital code-error calibration. The proposed ADC adopts a four-stage pipeline architecture to minimize power consumption and die area and employs a digital calibration technique in the front-end stage MDAC without any modification of critical analog circuits. The front-end MDAC code errors due to device mismatch are measured by un-calibrated back-end three stages and stored in memory. During normal conversion, the stored code errors are recalled for code-error calibration in the digital domain. The signal insensitive 3-D fully symmetric layout technique in three MDACs is employed to achieve a high matching accuracy and to measure the mismatch error of the front-end stage more exactly. The prototype ADC in a 0.18um CMOS process demonstrates a measured DNL and INL within 0.78LSB and 3.28LSB. The ADC, with an active die area of $4.2mm^2$, shows a maximum SNDR and SFDR of 67.2dB and 79.5dB, respectively, and a power consumption of 225mW at 2.5V and 50MS/s.