Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers

( Sejoon Lee ),( Kil-yong Lee ),( Ji-hwan Park ),( Duck-woo Kim ),( Heung-kwon Oh ),( Seong-taek Oh ),( Jongbum Jeon ),( Dongyoon Lee ),( Soobok Joe ),( Hoang Bao Khanh Chu ),( Jisun Kang ),( Jin-youn 생화학분자생물학회 2024 BMB Reports Vol.57 No.3

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5’ untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis. [BMB Reports 2024; 57(3): 161-166]

Predicting disease phenotypes based on the molecular networks with condition-responsive correlation.

Lee, Sejoon,Lee, Eunjung,Lee, Kwang H,Lee, Doheon Inderscience 2011 International journal of data mining and bioinform Vol.5 No.2

<P>Network-based methods using molecular interaction networks integrated with gene expression profiles have been proposed to solve problems, which arose from smaller number of samples compared with the large number of predictors. However, previous network-based methods, which have focused only on expression levels of proteins, nodes in the network through the identification of condition-responsive interactions. We propose a novel network-based classification, which focuses on both nodes with discriminative expression levels and edges with Condition-Responsive Correlations (CRCs) across two phenotypes. We found that modules with condition-responsive interactions provide candidate molecular models for diseases and show improved performances compared conventional gene-centric classification methods.</P>

Building the process-drug–side effect network to discover the relationship between biological Processes and side effects

Lee, Sejoon,Lee, Kwang H,Song, Min,Lee, Doheon BioMed Central 2011 BMC bioinformatics Vol.12 No.suppl2

<P><B>Background</B></P><P>Side effects are unwanted responses to drug treatment and are important resources for human phenotype information. The recent development of a database on side effects, the side effect resource (SIDER), is a first step in documenting the relationship between drugs and their side effects. It is, however, insufficient to simply find the association of drugs with biological processes; that relationship is crucial because drugs that influence biological processes can have an impact on phenotype. Therefore, knowing which processes respond to drugs that influence the phenotype will enable more effective and systematic study of the effect of drugs on phenotype. To the best of our knowledge, the relationship between biological processes and side effects of drugs has not yet been systematically researched.</P><P><B>Methods</B></P><P>We propose 3 steps for systematically searching relationships between drugs and biological processes: enrichment scores (ES) calculations, t-score calculation, and threshold-based filtering. Subsequently, the side effect-related biological processes are found by merging the drug-biological process network and the drug-side effect network. Evaluation is conducted in 2 ways: first, by discerning the number of biological processes discovered by our method that co-occur with Gene Ontology (GO) terms in relation to effects extracted from PubMed records using a text-mining technique and second, determining whether there is improvement in performance by limiting response processes by drugs sharing the same side effect to frequent ones alone.</P><P><B>Results</B></P><P>The multi-level network (the process-drug-side effect network) was built by merging the drug-biological process network and the drug-side effect network. We generated a network of 74 drugs-168 side effects-2209 biological process relation resources. The preliminary results showed that the process-drug-side effect network was able to find meaningful relationships between biological processes and side effects in an efficient manner.</P><P><B>Conclusions</B></P><P>We propose a novel process-drug-side effect network for discovering the relationship between biological processes and side effects. By exploring the relationship between drugs and phenotypes through a multi-level network, the mechanisms underlying the effect of specific drugs on the human body may be understood.</P>

NGSCheckMate: software for validating sample identity in next-generation sequencing studies within and across data types

Lee, Sejoon,Lee, Soohyun,Ouellette, Scott,Park, Woong-Yang,Lee, Eunjung A.,Park, Peter J. Oxford University Press 2017 Nucleic acids research Vol.45 No.11

<P><B>Abstract</B></P><P>In many next-generation sequencing (NGS) studies, multiple samples or data types are profiled for each individual. An important quality control (QC) step in these studies is to ensure that datasets from the same subject are properly paired. Given the heterogeneity of data types, file types and sequencing depths in a multi-dimensional study, a robust program that provides a standardized metric for genotype comparisons would be useful. Here, we describe NGSCheckMate, a user-friendly software package for verifying sample identities from FASTQ, BAM or VCF files. This tool uses a model-based method to compare allele read fractions at known single-nucleotide polymorphisms, considering depth-dependent behavior of similarity metrics for identical and unrelated samples. Our evaluation shows that NGSCheckMate is effective for a variety of data types, including exome sequencing, whole-genome sequencing, RNA-seq, ChIP-seq, targeted sequencing and single-cell whole-genome sequencing, with a minimal requirement for sequencing depth (>0.5X). An alignment-free module can be run directly on FASTQ files for a quick initial check. We recommend using this software as a QC step in NGS studies. Availability: https://github.com/parklab/NGSCheckMate</P>

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort

Jaeim Lee,Jong-Hwan Kim,Hoang Bao Khanh Chu,Seong-Taek Oh,Sung-Bum Kang,Sejoon Lee,Duck-Woo Kim,Heung-Kwon Oh,Ji-Hwan Park,Jisu Kim,Jisun Kang,Jin-Young Lee,Sheehyun Cho,Hyeran Shim,Hong Seok Lee,Seon Korean Society for Molecular and Cellular Biology 2024 Molecules and cells Vol.47 No.3

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort

Kil-yong Lee,Jaeim Lee,Jong Hwan Kim,Hoang Bao Khanh Chu,Seong-Taek Oh,Sung-Bum Kang,Sejoon Lee,Duck-Woo Kim,Heung-Kwon Oh,Ji-Hwan Park,Ji-Su Kim,Jisun Kang,Jin-Young Lee,Sheehyun Cho,심혜란,Hong Seok Le 한국분자세포생물학회 2024 Molecules and cells Vol.47 No.1

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

Observation of Single Electron Transport via Multiple Quantum States of a Silicon Quantum Dot at Room Temperature

Lee, Sejoon,Lee, Youngmin,Song, Emil B.,Hiramoto, Toshiro American Chemical Society 2014 NANO LETTERS Vol.14 No.1

<P>Single electron transport through multiple quantum levels is realized in a Si quantum-dot device at room-temperature conditions. The energy spacing of more than triple the omnipresent thermal energy is obtained from an extremely small ellipsoidal Si quantum dot, and high charge stability is attained through a construction of the gate-all-around structure. These properties may move us a step closer to practical applications of quantum devices at elevated temperatures. An in-depth analysis on the transport behavior and quantum structure is presented.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/nalefd/2014/nalefd.2014.14.issue-1/nl403204k/production/images/medium/nl-2013-03204k_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nl403204k'>ACS Electronic Supporting Info</A></P>

Thermodynamic Behavior of Excitonic Emission Properties in Manganese- and Zinc-Codoped Indium Phosphide Diluted Magnetic Semiconductor Layers

Lee, Sejoon,Song, Emil B.,Wang, Kang L.,Yoon, Chong S.,Yoon, Im Taek,Shon, Yoon,Kang, Tae Won American Chemical Society 2011 The Journal of Physical Chemistry Part C Vol.115 No.47

<P>The thermodynamic behavior of excitonic emission properties in manganese- and zinc-codoped indium phosphide (InMnP:Zn) diluted magnetic semiconductor (DMS) layers was investigated. Compared to the InMnP:Zn DMS layer (Mn ≈ 0.06%), the inhomogeneous thermal-broadening of the excitonic-emission line-width in InMnP:Zn DMS layer (Mn ≈ 0.29%) is dominant at lower temperatures. This is attributed to the increase of ionized impurity scattering from Mn ions and results in the increase of exciton–phonon coupling strength. As a consequence, high Mn content can lead to low excitonic emission efficiency, although generally a larger Mn content is favorable to increase the Curie temperature of a DMS material.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2011/jpccck.2011.115.issue-47/jp207879b/production/images/medium/jp-2011-07879b_0006.gif'></P>

Tuning of electrical charging effects for ferromagnetic Mn-doped ZnO nanocrystals embedded into a SiO2 layer fabricated by KrF excimer laser irradiation

Lee, Sejoon,Kim, Deuk Young,Won Kang, Tae,Cho, Hyung Koun American Institute of Physics 2009 JOURNAL OF APPLIED PHYSICS - Vol.106 No.2

Multiple logic functions from extended blockade region in a silicon quantum-dot transistor

Lee, Youngmin,Lee, Sejoon,Im, Hyunsik,Hiramoto, Toshiro American Institute of Physics 2015 Journal of Applied Physics Vol.117 No.6