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The Importance of Standardization on Analyzing Circulating RNA

Inyoul Lee, David Baxter, Min Young Lee, Kelsey Scherler, Kai Wang
2016 Molecular Diagnosis & Therapy  
Lee et al. Page 15 Author Manuscript Author Manuscript Author Manuscript Author Manuscript Author Manuscript Author Manuscript Author Manuscript Author Manuscript Lee et al.  ... 
doi:10.1007/s40291-016-0251-y pmid:28039578 pmcid:PMC5426982 fatcat:56s42d6l6narze4mp6lhnxubda

Recent Advances in RNA Therapy and Its Carriers to Treat the Single-Gene Neurological Disorders

Ming-Jen Lee, Inyoul Lee, Kai Wang
2022 Biomedicines  
.), and also grants from the Ministry of Science and Technology, Taiwan, MOST 109-2314-B-002 -121 -MY3 (Lee, M-J) and the National Taiwan University Hospital, NTUH 111-S0204 (Lee, M-J).Institutional Review  ... 
doi:10.3390/biomedicines10010158 pmid:35052837 pmcid:PMC8773368 fatcat:yjhtl2rkijd27jtwnklc7v6xti

Extracellular microRNA: A new source of biomarkers

Alton Etheridge, Inyoul Lee, Leroy Hood, David Galas, Kai Wang
2011 Mutation research  
doi:10.1016/j.mrfmmm.2011.03.004 pmid:21540043 pmcid:PMC3199035 fatcat:t6p4xhce5bedzbkryxquiasohu

A Systems Approach to Rheumatoid Arthritis

Sungyong You, Chul-Soo Cho, Inyoul Lee, Leroy Hood, Daehee Hwang, Wan-Uk Kim, Michael A. Mancini
2012 PLoS ONE  
OA FLS or reference mRNA samples; see Table 1 ), as described in Lee et al. [32] . We then denoted these genes in the RA-perturbed network.  ... 
doi:10.1371/journal.pone.0051508 pmid:23240033 pmcid:PMC3519858 fatcat:f5bh4izfnrextphhix7mir67oq

Systems Biology and the Discovery of Diagnostic Biomarkers

Kai Wang, Inyoul Lee, George Carlson, Leroy Hood, David Galas
2010 Disease Markers  
Systems biology is an approach to the science that views biology as an information science, studies biological systems as a whole and their interactions with the environment. This approach, for the reasons described here, has particular power in the search for informative diagnostic biomarkers of diseases because it focuses on the fundamental causes and keys on the identification and understanding of disease- perturbed molecular networks. In this review, we describe some recent developments
more » ... have used systems biology to address complex diseases – prion disease and drug induced liver injury- and use these as examples to illustrate the importance of understanding network structure and dynamics. The knowledge of network dynamics through in vitro experimental perturbation and modeling allows us to determine the state of the networks, to identify molecular correlates, and to derive new disease treatment approaches to reverse the pathology or prevent its progress into a more severe state through the manipulation of network states. This general approach, including diagnostics and therapeutics, is becoming known as systems medicine.
doi:10.1155/2010/130861 pmid:20534905 pmcid:PMC3021550 fatcat:5yht7afxazazvnptmzqonoz3va

Comparative Genomics of the Human and Mouse T Cell Receptor Loci

Gustavo Glusman, Lee Rowen, Inyoul Lee, Cecilie Boysen, Jared C. Roach, Arian F.A. Smit, Kai Wang, Ben F. Koop, Leroy Hood
2001 Immunity  
and J elements. The V elements are classified into subfamilies whose members are ‫%07ف‬ to 100% identical. There are three hypervariable regions in each TCR poly-,5 peptide that fold to create the antigen binding site. The third hypervariable site is encoded by the region repre-1 The Institute for Systems Biology 4225 Roosevelt Way NE senting the joined V, (D), and J elements. Recombination signals, canonically considered to be nonamers and Seattle, Washington 98105 2 Paracel Inc. heptamers
more » ... rated by spacers of 12 or 23 nucleotides, are found at the 3Ј end of the V elements, the 5Ј of the 1055 East Colorado Boulevard Pasadena, California 91106 J elements, and on both sides of the D elements. Four distinct mechanisms contribute to the diversity of T cell 3 Phenogenomics Corporation 22026 20 th Avenue SE, Suite 101 receptor molecules: (1) multiple germline V, D, and J elements; (2) combinatorial joining of the V, D, and J Bothell, Washington 98021 4 Department of Biology elements within a family; (3) nibbling by exonuclease and/or nucleotide addition by terminal deoxynucleotidyl University of Victoria Victoria, British Columbia transferase during the rearrangement process to create enormous diversity in the third hypervariable region (this Canada V8W 3N5 is termed N region diversity); and (4) the ␣ and ␤ or ␥ and ␦ chains may be paired in different combinations-a process termed combinatorial association. Summary In 1990 , we initiated a pilot sequencing project to test the feasibility of sequencing large gene families in the The availability of the complete genomic sequences of the human and mouse T cell receptor loci opens up human genome. The aim was to determine the complete nucleotide sequences of the human and mouse T cell new opportunities for understanding T cell receptors (TCRs) and their genes. The full complement of TCR receptor loci: ␣/␦, ␤, and ␥ (Figure 1). These comparative studies would open up new opportunities for under-gene segments is finally known and should prove a valuable resource for supporting functional studies. A standing T cell receptors and their genes. A delineation of the number and sequences of V elements and their rational nomenclature system has been implemented and is widely available through IMGT and other public comparison against T cell receptor cDNA sequences would allow an assessment of the relative contributions databases. Systematic comparisons of the genomic sequences within each locus, between loci, and across of the various diversification mechanisms. The promoter sequences of the V elements could be analyzed to species enable precise analyses of the various diversification mechanisms and some regulatory signals. The search for shared motifs. The genomic landscape of these gene families could be delineated, including the genomic landscape of the TCR loci provides fundamental insights into TCR evolution as highly localized number and spacing of T cell receptor elements, GϩC content, repeat sequences, and other genes. Finally, and tightly regulated gene families. through the comparisons of these gene families in mouse and human, fundamental insights into the evolu-Introduction The cellular immune system visualizes the world of tion of these gene families could be obtained. pathogens largely through its T cell immune receptors. T cell receptors (TCRs) are of two types: ␣␤ and ␥␦. Overview The ␣␤ TCRs recognize peptide fragments presented Genomic Landscape by class I or class II molecules of the major histocompati-Analysis of the genomic sequence encompassing the bility complex (MHC), whereas the ␥␦ TCRs may recoghuman and mouse TCR loci revealed that the elements nize free peptides. Each T cell only expresses one type of the TCR genes are distributed across hundreds of of T cell receptor. T cell receptor monomers are encoded kilobases (kb) of genomic sequence, ranging from less by four distinct gene families: ␣, ␤, ␥, and ␦, contained than 200 kb for TCR ␥ to over 1 Mb for the combined within three chromosomal loci: ␣/␦, ␤, and ␥. Regions TCR ␣/␦ locus (Figure 1) . Nevertheless, the "TCR subof the T cell receptor polypeptides are classified into genome" (the fraction of the genome devoted to TCR variable regions capable of recognizing foreign molecugenes) is fairly compact, claiming less than 0.1% of the lar patterns and constant regions that anchor the recepgenome. tors in the T cell membrane. The variable regions are In both the TCR ␣/␦ and ␤ loci, other gene families encoded by several distinct DNA elements that are reare interspersed among the TCR elements (Figure 1 ). arranged and joined during T cell differentiation: for the The 5Ј end of the TCR ␣ locus shows some intermixing ␤ and ␦ polypeptides-variable (V), diversity (D), and with olfactory receptor genes, while the TCR ␤ locus joining (J) elements; and for the ␣ and ␥ polypeptides-V encodes trypsinogen genes that flank the 5Ј and 3Ј ends of the array of V elements. These gene associations have existed for more than 300 million years, as reflected 5 Correspondence: lhood@systemsbiology.org 6 These authors contributed equally to this work. by their conserved relationships in the human, mouse,
doi:10.1016/s1074-7613(01)00200-x pmid:11567625 fatcat:oolfyw5okvhmtlsp2fdjxaaulu

Core transcriptional regulatory circuits in prion diseases

Taek-Kyun Kim, Inyoul Lee, Ji-Hoon Cho, Brenda Canine, Andrew Keller, Nathan D. Price, Daehee Hwang, George Carlson, Leroy Hood
2020 Molecular Brain  
Complex diseases involve dynamic perturbations of pathophysiological processes during disease progression. Transcriptional programs underlying such perturbations are unknown in many diseases. Here, we present core transcriptional regulatory circuits underlying early and late perturbations in prion disease. We first identified cellular processes perturbed early and late using time-course gene expression data from three prion-infected mouse strains. We then built a transcriptional regulatory
more » ... rk (TRN) describing regulation of early and late processes. We found over-represented feed-forward loops (FFLs) comprising transcription factor (TF) pairs and target genes in the TRN. Using gene expression data of brain cell types, we further selected active FFLs where TF pairs and target genes were expressed in the same cell type and showed correlated temporal expression changes in the brain. We finally determined core transcriptional regulatory circuits by combining these active FFLs. These circuits provide insights into transcriptional programs for early and late pathophysiological processes in prion disease.
doi:10.1186/s13041-020-0551-3 pmid:31959236 fatcat:weaqz3hdvzb6zgk4lrpnxgdiom

Issues and Prospects of microRNA-Based Biomarkers in Blood and Other Body Fluids

John Chevillet, Inyoul Lee, Hilary Briggs, Yuqing He, Kai Wang
2014 Molecules  
Cell-free circulating microRNAs (miRNAs) in the blood are good diagnostic biomarker candidates for various physiopathological conditions, including cancer, neurodegeneration, diabetes and other diseases. Since their discovery in 2008 as blood biomarkers, the field has expanded rapidly with a number of important findings. Despite the initial optimistic views of their potential for clinical application, there are currently no circulating miRNA-based diagnostics in use. In this article, we review
more » ... he status of circulating miRNAs, examine different analytical approaches, and address some of the challenges and opportunities.
doi:10.3390/molecules19056080 pmid:24830712 fatcat:mmyxzmtjbzcv3mg4rthrimousu

Systems Biology and the Emergence of Systems Medicine [chapter]

Nathan D. Price, Lucas B. Edelman, Inyoul Lee, Hyuntae Yoo, Daehee Hwang, George Carlson, David J. Galas, James R. Heath, Leroy Hood
2009 Genomic and Personalized Medicine  
., 2003; Lee et al., 2006) . In practice, however, the task of identifying markers of disease states in the vast array of secreted proteins can seem daunting.  ...  basis for the very broad range of blood biomarker studies that are being carried out by many scientific centers (Anderson and Anderson, 2002; Fujii et al., 2004; Hood et al., 2004; Lathrop et al., 2003; Lee  ... 
doi:10.1016/b978-0-12-369420-1.00006-8 fatcat:fm622l36m5fj5gun6yqn3gttni

Performance of Korean Soybean Varieties in Indonesia

Heru Kuswantoro, Sutrisno Sutrisno, Won-Young Han, Poong-Yeon Lee, Yang-Hee Cho, InYoul Baek
2014 Journal of the Korean Society of International Agriculture  
**, Yang-Hee Cho**, and InYoul Baek* 1 , Jangmikong, and Songhakkong, i.e. 12.8 g, 11.6 g, 11.4 g, and 11.3 g per plant respectively.  ...  indirect approach to selection criteria for seed yield tends to be more effective than Performance of Korean Soybean Varieties in Indonesia Heru Kuswantoro, Sutrisno, Won-Young Han* † , Poong-Yeon Lee  ... 
doi:10.12719/ksia.2014.26.2.107 fatcat:wo3w3tiavjf65miisxg46p7jda

A systems approach to prion disease

Daehee Hwang, Inyoul Y Lee, Hyuntae Yoo, Nils Gehlenborg, Ji-Hoon Cho, Brianne Petritis, David Baxter, Rose Pitstick, Rebecca Young, Doug Spicer, Nathan D Price, John G Hohmann (+3 others)
2009 Molecular Systems Biology  
Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrP C ) to disease-causing PrP Sc isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain-prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host
more » ... enetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrP Sc replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches. a End point is equivalent to the incubation time in this study, which is defined as the interval between prion inoculation to end point. With the exception of 0/0 mice, all animals were at the terminal stages of disease when killed for brain harvest. For each combination, a set of mice was inoculated with brain homogenate from normal mice and brains were harvested at the same time points as prion-infected mice. b Brains from three mice were taken at each time point. In a few instances, the interval deviated from that shown. For example, the final interval for B6-RML was 1 week due to severity of illness in these mice. The actual intervals are indicated in figures that follow. c Additional three RML-inoculated and three normal brain homogenate-inoculated 0/0 mice were aged 357 days (51 weeks).
doi:10.1038/msb.2009.10 pmid:19308092 pmcid:PMC2671916 fatcat:u7t2unnckzhwvkeaau64eqpvlu

Distinct Profiles of Cell-Free MicroRNAs in Plasma of Veterans with Post-Traumatic Stress Disorder

Min Young Lee, David Baxter, Kelsey Scherler, Taek-Kyun Kim, Xiaogang Wu, Duna Abu-Amara, Janine Flory, Rachel Yehuda, Charles Marmar, Marti Jett, Inyoul Lee, Kai Wang (+1 others)
2019 Journal of Clinical Medicine  
Dysregulation of circulating microRNAs (miRNAs) in body fluids has been reported in psychiatric disorders such as schizophrenia, bipolar disorder, major depressive disorder, and post-traumatic stress disorder (PTSD). Recent studies of various diseases showed that extracellular vesicles (EV) in body fluids can provide different spectra of circulating miRNAs and disease-associated signatures from whole fluid or EV-depleted fraction. However, the association of miRNAs in EVs to PTSD has not been
more » ... udied. In this study, we performed a comprehensive profiling of miRNAs in whole plasma, extracellular vesicles (EV) and EV-depleted plasma (EVD) samples collected from combat veterans with PTSD and matched controls by utilizing a next-generation sequencing (NGS) platform. In total, 520 circulating miRNAs were quantified from 24 male Iraq and Afghanistan combat veterans with (n = 12) and without (n = 12) PTSD. The overall miRNA profiles in whole plasma, EV and EVD fractions were different and miRNAs affected by PTSD were also distinct in each sample type. The concentration changes of miR-203a-3p in EV and miR-339-5p in EVD were confirmed in an independent validation cohort that consisted of 20 veterans (10 with and 10 without PTSD) using qPCR. The target genes of these two miRNAs were involved in signaling pathways and comorbid conditions associated with PTSD (e.g., neurotransmitter systems such as dopaminergic and serotonergic signaling, inflammatory response, and cardiovascular diseases). Our findings suggest that PTSD may have different impacts on miRNAs encapsulated in vesicles and outside of vesicles. Further studies using larger samples are needed to evaluate the utility of these miRNAs as diagnostic biomarkers for PTSD.
doi:10.3390/jcm8070963 pmid:31277223 pmcid:PMC6678393 fatcat:djvyajzgnvgvnmkdvqd2dotvcq

A New Soybean Variety, 'Joongmo 3009' with Green Cotyledon, Black Seed Coat, Disease Tolerant, and High Yield

Won-Young Han, Hyun-Tae Kim, Jong-Min Ko, Hong-Tae Yun, InYoul Baek, Byung-Won Lee, Young-Hoon Lee, Tae-Jung Ha, Sang-Ouk Shin, Suk-Ki Lee, Chan-Sik Jung, Jae-Keun Choi (+5 others)
2016 Korean Journal of Breeding Science  
A new soybean variety, 'Joongmo 3009' (Milyang 222) was developed at the National Institute of Crop Science (NICS) in 2012. 'Joongmo 3009' was released by pedigree selection from the cross between 'Cheongja 2(Milyang 121)' and 'Daemangkong'. It has determinate growth habit, white flower, brown pubescence, brown pod color, green seed coat, green cotyledon, spherical seed shape, oval leaf shape and large seed size (29.3 grams per 100 seeds). It was late 16 days in maturing date than the check
more » ... ivar 'Cheongjakong'. The average yield of 'Joongmo 3009' was 2.91 ton per hectare, which was higher 36 percentage than the check variety, in the regional yield trials carried out in three adaptable locations of Korea from 2010 to 2012. The number of breeder's right is '5474'
doi:10.9787/kjbs.2016.48.1.054 fatcat:brax6y5dcza3phihf7gublztym

Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice

Sarah R. Anderson, Inyoul Lee, Christine Ebeling, Dennis A. Stephenson, Kelsey M. Schweitzer, David Baxter, Tara M. Moon, Sarah LaPierre, Benjamin Jaques, Derek Silvius, Michael Wegner, Leroy E. Hood (+2 others)
2014 Mammalian Genome  
Mice homozygous for the gray tremor (gt) mutation have a pleiotropic phenotype that includes pigmentation defects, megacolon, whole body tremors, sporadic seizures, hypo-and dysmyelination of the CNS and PNS, vacuolation of the CNS, and early death. Vacuolation similar to that caused by prions was originally reported to be transmissible, but subsequent studies showed the inherited disease was not infectious. The gt mutation mapped to distal mouse chromosome 15, to the same region as Sox10,
more » ... encodes a transcription factor with essential roles in neural crest survival and differentiation. As dominant mutations in mouse or human SOX10 cause white spotting and intestinal aganglionosis, we screened the Sox10 coding region for mutations in gt/gt DNA. An adenosine to guanine transversion was identified in exon 2 that changes a highly conserved glutamic acid residue in the SOX10 DNA binding domain to glycine. This mutant allele was not seen in wildtype mice, including the related GT/Le strain, and failed to complement a Sox10 null allele. Gene expression analysis revealed significant down-regulation of genes involved in myelin lipid biosynthesis pathways in gt/gt brains. Knockout mice for some of these genes develop CNS vacuolation and/or myelination defects, suggesting that their downregulation may contribute to these phenotypes in gt mutants and could underlie the neurological phenotypes associated with Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung (PCWH) disease, caused by mutations in human SOX10.
doi:10.1007/s00335-014-9548-5 pmid:25399070 pmcid:PMC4305468 fatcat:drdweade2jev3fklpqlxl6dxva

Principal network analysis: identification of subnetworks representing major dynamics using gene expression data

Yongsoo Kim, Taek-Kyun Kim, Yungu Kim, Jiho Yoo, Sungyong You, Inyoul Lee, George Carlson, Leroy Hood, Seungjin Choi, Daehee Hwang
2010 Computer applications in the biosciences : CABIOS  
Conversion of the weight matrix to a non-negative matrix A non-negative matrix factorization (NMF; Lee and Seung, 1999) requires the input matrix to be non-negative.  ...  Application of Orthogonal NMF to the weight matrix Orthogonal non-negative matrix factorization (ONMF) Given a non-negative matrix X con (N × M), the NMF (Lee and Seung, 1999) iteratively computes  ... 
doi:10.1093/bioinformatics/btq670 pmid:21193522 pmcid:PMC3031040 fatcat:doczw3zryba3dlhyaxnkq3gjzq
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