Introduction: Colorectal mucinous adenocarcinoma (MC) differs from adenocarcinoma (AD) in clinical features and molecular characteristics. The current treatment of colorectal MC is not precise enough, and the molecular characteristics remain unclear. The study aims to explore the difference between colorectal MC and AD on the transcriptome level for the possibility of treating colorectal MC precisely. Methods: The data of colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database was assessed, and then differential analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify the differential hub RNAs between colorectal MC and AD. Differential hub lncRNAs and hub RNA of significant modules were validated by quantitative real-time PCR (qRT-PCR) among different colon cancer cell lines. Results: In total, 1680 differential expressed RNAs (DERs) were found by comparing colorectal MC (52, 13.3%) with AD (340, 86.7%). Through the WGCNA, a mucin-associated RNA module was identified, while some others might be associated with unique immune progress. Finally, 6 differential hub RNAs in the mucin-associated RNA module (CTD-2589M5.4, RP11-234B24.2, RP11-25K19.1 and COLCA1) were validated by qRT-PCR and showed higher expression levels in mucin-producing colorectal cell lines (Ls174T and HT-29). Conclusion: This study suggests that clinical treatments for colorectal MC should be differentiated from AD. Further exploration of enterocyte (goblet cell) differentiation with tumor genesis and the distinct immune progression of MC may help to identify key therapeutic targets for colorectal MC. Further research on the application of immunotherapy to colorectal MC is needed.
导言:结直肠粘液腺癌(MC)与腺癌(AD)在临床特征和分子特征上有所不同。目前对结直肠黏液腺癌的治疗不够精确,其分子特征仍不明确。本研究旨在探讨结直肠MC与AD在转录组水平上的差异,为精确治疗结直肠MC提供可能。研究方法评估癌症基因组图谱(TCGA)数据库中结直肠癌(CRC)患者的数据,然后进行差异分析和加权基因共表达网络分析(WGCNA),以确定结直肠MC和AD之间的差异中枢RNA。在不同的结肠癌细胞系中,通过实时定量 PCR(qRT-PCR)验证了差异中枢 lncRNA 和重要模块的中枢 RNA。结果显示通过比较结直肠癌 MC(52 个,占 13.3%)和结直肠癌 AD(340 个,占 86.7%),总共发现了 1680 个差异表达 RNA(DER)。通过 WGCNA,发现了一个与粘蛋白相关的 RNA 模块,而其他一些 RNA 可能与独特的免疫进展有关。最后,通过 qRT-PCR 验证了粘蛋白相关 RNA 模块中的 6 个差异中枢 RNA(CTD-2589M5.4、RP11-234B24.2、RP11-25K19.1 和 COLCA1),它们在产生粘蛋白的结直肠细胞系(Ls174T 和 HT-29)中的表达水平较高。结论本研究表明,结直肠 MC 的临床治疗应与 AD 区分开来。进一步探讨肠细胞(鹅口疮细胞)分化与肿瘤发生以及 MC 独特的免疫进展可能有助于确定结直肠 MC 的关键治疗靶点。还需要进一步研究免疫疗法在结直肠癌 MC 中的应用。
{"title":"Transcriptomic Landscape of Colorectal Mucinous Adenocarcinoma has Similarity with Intestinal Goblet Cell Differentiation","authors":"Jianbo Liu, Siyuan Qiu, Xiaorui Fu, Bin Zhou, Ruijuan Zu, Zhaoying Lv, Yuan Li, Lie Yang, Zongguang Zhou","doi":"10.2174/0113892029312303240821080358","DOIUrl":"https://doi.org/10.2174/0113892029312303240821080358","url":null,"abstract":"Introduction: Colorectal mucinous adenocarcinoma (MC) differs from adenocarcinoma (AD) in clinical features and molecular characteristics. The current treatment of colorectal MC is not precise enough, and the molecular characteristics remain unclear. The study aims to explore the difference between colorectal MC and AD on the transcriptome level for the possibility of treating colorectal MC precisely. Methods: The data of colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database was assessed, and then differential analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify the differential hub RNAs between colorectal MC and AD. Differential hub lncRNAs and hub RNA of significant modules were validated by quantitative real-time PCR (qRT-PCR) among different colon cancer cell lines. Results: In total, 1680 differential expressed RNAs (DERs) were found by comparing colorectal MC (52, 13.3%) with AD (340, 86.7%). Through the WGCNA, a mucin-associated RNA module was identified, while some others might be associated with unique immune progress. Finally, 6 differential hub RNAs in the mucin-associated RNA module (CTD-2589M5.4, RP11-234B24.2, RP11-25K19.1 and COLCA1) were validated by qRT-PCR and showed higher expression levels in mucin-producing colorectal cell lines (Ls174T and HT-29). Conclusion: This study suggests that clinical treatments for colorectal MC should be differentiated from AD. Further exploration of enterocyte (goblet cell) differentiation with tumor genesis and the distinct immune progression of MC may help to identify key therapeutic targets for colorectal MC. Further research on the application of immunotherapy to colorectal MC is needed.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of a cancer vaccine comes with its complications and designing and developing a vaccine against foreign invaders such as bacterial and viral particles is not as complex and multi-faceted as the preparation of immunotherapy for host-infected cells which resemble our own body cells. The entire research and development framework of designing a vaccine for cancerous cells lies entirely on the remarkable aspect of notifying specific interactions and acclimatising the immune system. This review aims to compile the several fronts research-based methodology applies to in terms of developing a therapeutic, preventive or personalised vaccine for cancer . The approach lays focus on the identification and selection of targets for vaccine development which have come to light as immune biomarkers. Furthemore, significant aspects of personalised and precision vaccines and the fine line that runs between these approaches have also been discussed.
{"title":"An Insight into Immunological Therapeutic Approach against Cancer: Potential Anti-Cancer Vaccines","authors":"Arjun Singh Kohli, Somali Sanyal, Radhey Shyam Kaushal, Manish Dwivedi","doi":"10.2174/0113892029319505240821063238","DOIUrl":"https://doi.org/10.2174/0113892029319505240821063238","url":null,"abstract":"The development of a cancer vaccine comes with its complications and designing and developing a vaccine against foreign invaders such as bacterial and viral particles is not as complex and multi-faceted as the preparation of immunotherapy for host-infected cells which resemble our own body cells. The entire research and development framework of designing a vaccine for cancerous cells lies entirely on the remarkable aspect of notifying specific interactions and acclimatising the immune system. This review aims to compile the several fronts research-based methodology applies to in terms of developing a therapeutic, preventive or personalised vaccine for cancer . The approach lays focus on the identification and selection of targets for vaccine development which have come to light as immune biomarkers. Furthemore, significant aspects of personalised and precision vaccines and the fine line that runs between these approaches have also been discussed.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.2174/0113892029314148240820082402
Jeong Sun Park, Jina Kim, Yeha Kim, Ki Hwan Kim, Woori Kwak, Iksoo Kim
Background: The blackish cicada (Cryptotympana atrata) exhibits unique characteristics and is one of the model cicadas found in the Korean Peninsula. It is a species of southern origin, prefers high temperatures, and is listed as a climate-sensitive indicator species in South Korea. Therefore, this species can be utilized to study the impact of climate change on the genetic diversity and structure of populations. However, research on the genome of C. atrata is limited. Methods: We sequenced the genome of an individual collected from South Korea and constructed a draft genome. Additionally, we collected ten specimens from each of the five regions in South Korea and identified single nucleotide variants (SNVs) for population genetic analysis. The sequencing library was constructed using the MGIEasy DNA Library Prep Kit and sequenced using the MGISEQ-2000 platform with 150-bp paired-end reads. Results: The draft genome of C. atrata was approximately 5.0 Gb or 5.2 Gb, making it one of the largest genomes among insects. Population genetic analysis, which was conducted on four populations in South Korea, including both previously distributed and newly expanded regions, showed that Jeju Island, a remote southern island with the highest average temperature, formed an independent genetic group. However, there were no notable genetic differences among the inland populations selected based on varying average temperatures, indicating that the current population genetic composition on the Korean Peninsula is more reflective of biogeographic history rather than climate- induced genetic structures. Additionally, we unexpectedly observed that most individuals of C. atrata collected in a specific locality were infected with microbes not commonly found in insects, necessitating further research on the pathogens within C. atrata. Conclusion: This study introduces the draft genome of C. atrata, a climate-sensitive indicator species in South Korea. Population analysis results indicate that the current genetic structure of C. atrata is driven by biogeographic history rather than just climate. The prevalence of widespread pathogen infections raises concerns about their impact on C. atrata. Considering the scarcity of publicly available genomic resources related to the family Cicadidae, this draft genome and population data of C. atrata are expected to serve as a valuable resource for various studies utilizing cicada genomes.
背景:黑蝉(Cryptotympana atrata)具有独特的特征,是朝鲜半岛发现的模范蝉之一。它原产于南方,喜欢高温,在韩国被列为气候敏感指示物种。因此,该物种可用于研究气候变化对种群遗传多样性和结构的影响。然而,对 C. atrata 基因组的研究还很有限。方法:我们对从韩国采集的一个个体进行了基因组测序,并构建了基因组草案。此外,我们还从韩国的五个地区各采集了十个标本,并鉴定了单核苷酸变体(SNV),用于种群遗传分析。我们使用 MGIEasy DNA 文库制备试剂盒构建了测序文库,并使用 MGISEQ-2000 平台对 150-bp 的成对端读数进行了测序。结果C. atrata的基因组草案约为5.0 Gb或5.2 Gb,是昆虫中最大的基因组之一。对韩国的四个种群(包括以前分布的地区和新扩展的地区)进行的种群遗传分析表明,平均气温最高的南部偏远岛屿济州岛形成了一个独立的遗传群体。然而,根据不同的平均气温选出的内陆种群之间并没有明显的遗传差异,这表明朝鲜半岛目前的种群遗传组成更多反映的是生物地理历史,而不是气候引起的遗传结构。此外,我们还意外地发现,在某一特定地点采集到的大多数姬蛙个体都感染了昆虫体内不常见的微生物,因此有必要对姬蛙体内的病原体进行进一步研究。结论本研究介绍了韩国气候敏感指示物种 C. atrata 的基因组草案。种群分析结果表明,C. atrata 目前的遗传结构是由生物地理历史而不仅仅是气候驱动的。大范围的病原体感染引发了对 C. atrata 影响的担忧。考虑到与蝉科相关的公开基因组资源稀缺,该蝉基因组草案和种群数据有望成为利用蝉基因组进行各种研究的宝贵资源。
{"title":"Whole Genome Sequences of Cryptotympana Atrata Fabricius, 1775 (Hemiptera: Cicadidae) in the Korean Peninsula: Insights into Population Structure with Novel Pathogenic Or Symbiotic Candidates","authors":"Jeong Sun Park, Jina Kim, Yeha Kim, Ki Hwan Kim, Woori Kwak, Iksoo Kim","doi":"10.2174/0113892029314148240820082402","DOIUrl":"https://doi.org/10.2174/0113892029314148240820082402","url":null,"abstract":"Background: The blackish cicada (Cryptotympana atrata) exhibits unique characteristics and is one of the model cicadas found in the Korean Peninsula. It is a species of southern origin, prefers high temperatures, and is listed as a climate-sensitive indicator species in South Korea. Therefore, this species can be utilized to study the impact of climate change on the genetic diversity and structure of populations. However, research on the genome of C. atrata is limited. Methods: We sequenced the genome of an individual collected from South Korea and constructed a draft genome. Additionally, we collected ten specimens from each of the five regions in South Korea and identified single nucleotide variants (SNVs) for population genetic analysis. The sequencing library was constructed using the MGIEasy DNA Library Prep Kit and sequenced using the MGISEQ-2000 platform with 150-bp paired-end reads. Results: The draft genome of C. atrata was approximately 5.0 Gb or 5.2 Gb, making it one of the largest genomes among insects. Population genetic analysis, which was conducted on four populations in South Korea, including both previously distributed and newly expanded regions, showed that Jeju Island, a remote southern island with the highest average temperature, formed an independent genetic group. However, there were no notable genetic differences among the inland populations selected based on varying average temperatures, indicating that the current population genetic composition on the Korean Peninsula is more reflective of biogeographic history rather than climate- induced genetic structures. Additionally, we unexpectedly observed that most individuals of C. atrata collected in a specific locality were infected with microbes not commonly found in insects, necessitating further research on the pathogens within C. atrata. Conclusion: This study introduces the draft genome of C. atrata, a climate-sensitive indicator species in South Korea. Population analysis results indicate that the current genetic structure of C. atrata is driven by biogeographic history rather than just climate. The prevalence of widespread pathogen infections raises concerns about their impact on C. atrata. Considering the scarcity of publicly available genomic resources related to the family Cicadidae, this draft genome and population data of C. atrata are expected to serve as a valuable resource for various studies utilizing cicada genomes.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-28DOI: 10.2174/0113892029331751240820111158
Zixin Duan, Yafeng Liang, Xin Xiu, Wenjie Ma, Hu Mei
Introduction: Ubiquitination, a unique post-translational modification, plays a cardinal role in diverse cellular functions such as protein degradation, signal transduction, DNA repair, and regulation of cell cycle. Method: Thus, accurate prediction of potential ubiquitination sites is an urgent requirement for exploring the ubiquitination mechanism as well as the disease pathogenesis associated with ubiquitination processes. Results: This study introduces a novel deep learning architecture, ResUbiNet, which utilized a protein language model (ProtTrans), amino acid properties, and BLOSUM62 matrix for sequence embedding and multiple state-of-the-art architectural components, i.e., transformer, multi-kernel convolution, residual connection, and squeeze-and-excitation for feature extractions. Conclusion: The results of cross-validation and external tests showed that the ResUbiNet model achieved better prediction performances in comparison with the available hCKSAAP_UbSite, RUBI, MDCapsUbi, and MusiteDeep models.
{"title":"ResUbiNet: A Novel Deep Learning Architecture for Ubiquitination Site Prediction","authors":"Zixin Duan, Yafeng Liang, Xin Xiu, Wenjie Ma, Hu Mei","doi":"10.2174/0113892029331751240820111158","DOIUrl":"https://doi.org/10.2174/0113892029331751240820111158","url":null,"abstract":"Introduction: Ubiquitination, a unique post-translational modification, plays a cardinal role in diverse cellular functions such as protein degradation, signal transduction, DNA repair, and regulation of cell cycle. Method: Thus, accurate prediction of potential ubiquitination sites is an urgent requirement for exploring the ubiquitination mechanism as well as the disease pathogenesis associated with ubiquitination processes. Results: This study introduces a novel deep learning architecture, ResUbiNet, which utilized a protein language model (ProtTrans), amino acid properties, and BLOSUM62 matrix for sequence embedding and multiple state-of-the-art architectural components, i.e., transformer, multi-kernel convolution, residual connection, and squeeze-and-excitation for feature extractions. Conclusion: The results of cross-validation and external tests showed that the ResUbiNet model achieved better prediction performances in comparison with the available hCKSAAP_UbSite, RUBI, MDCapsUbi, and MusiteDeep models.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.2174/0113892029317403240815044408
Nayeema Bulbul, Jinath Sultana, Ashrafus Safa, Md. Asaduzzaman Shishir, Bakhtiar Ul Islam, Md. Fakruddin, Md. Abu Bakar karim
Introduction: The gut microbiota plays a crucial role in maintaining human health, and probiotics have gained significant attention for their potential benefits. Among the diverse array of gut bacteria, Akkermansia muciniphila, and Lactobacillus spp. have emerged as promising candidates for their putative probiotic properties. Method: In this study, we conducted a comprehensive comparative in silico analysis of the genomes of A. muciniphila and Lactobacillus to decipher their probiotic potential. Utilizing a range of bioinformatics tools, we evaluated various genomic attributes, including functional gene content, metabolic pathways, antimicrobial peptide production, adhesion factors, and stress response elements. These findings revealed distinctive genomic signatures between the two genera. A. muciniphila genomes exhibited a high prevalence of mucin-degrading enzymes, suggesting a specialized adaptation for mucin utilization in the gut environment. Results: Additionally, the presence of specific pathways for short-chain fatty acid production highlighted its potential impact on host health. Lactobacillus genomes, on the other hand, demonstrated a diverse repertoire of functional genes associated with probiotic attributes, including the production of antimicrobial peptides and adhesion factors, indicating potential for host-microbe interactions and immune modulation. Furthermore, this analysis unveiled the genetic basis of stress tolerance in both genera, revealing conserved mechanisms for surviving the dynamic conditions of the gut ecosystem. Conclusion: This study also shed light on the distribution of antibiotic-resistance genes, allowing us to assess safety concerns associated with their potential use as probiotics. Overall, this comparative in silico exploration provides valuable insights into the genomic foundation of A. muciniphila and Lactobacillus probiotic potential. These findings contribute to the understanding of their respective roles within the gut microbiota and offer a foundation for further experimental investigations. As probiotic applications continue to expand, this study advances our knowledge of the genetic underpinnings that govern their functionality and highlights promising avenues for future therapeutic interventions and personalized health strategies.
{"title":"Genomic Face-Off: An In Silico Comparison of the Probiotic Potential of Lactobacillus spp. and Akkermansia muciniphila","authors":"Nayeema Bulbul, Jinath Sultana, Ashrafus Safa, Md. Asaduzzaman Shishir, Bakhtiar Ul Islam, Md. Fakruddin, Md. Abu Bakar karim","doi":"10.2174/0113892029317403240815044408","DOIUrl":"https://doi.org/10.2174/0113892029317403240815044408","url":null,"abstract":"Introduction: The gut microbiota plays a crucial role in maintaining human health, and probiotics have gained significant attention for their potential benefits. Among the diverse array of gut bacteria, Akkermansia muciniphila, and Lactobacillus spp. have emerged as promising candidates for their putative probiotic properties. Method: In this study, we conducted a comprehensive comparative in silico analysis of the genomes of A. muciniphila and Lactobacillus to decipher their probiotic potential. Utilizing a range of bioinformatics tools, we evaluated various genomic attributes, including functional gene content, metabolic pathways, antimicrobial peptide production, adhesion factors, and stress response elements. These findings revealed distinctive genomic signatures between the two genera. A. muciniphila genomes exhibited a high prevalence of mucin-degrading enzymes, suggesting a specialized adaptation for mucin utilization in the gut environment. Results: Additionally, the presence of specific pathways for short-chain fatty acid production highlighted its potential impact on host health. Lactobacillus genomes, on the other hand, demonstrated a diverse repertoire of functional genes associated with probiotic attributes, including the production of antimicrobial peptides and adhesion factors, indicating potential for host-microbe interactions and immune modulation. Furthermore, this analysis unveiled the genetic basis of stress tolerance in both genera, revealing conserved mechanisms for surviving the dynamic conditions of the gut ecosystem. Conclusion: This study also shed light on the distribution of antibiotic-resistance genes, allowing us to assess safety concerns associated with their potential use as probiotics. Overall, this comparative in silico exploration provides valuable insights into the genomic foundation of A. muciniphila and Lactobacillus probiotic potential. These findings contribute to the understanding of their respective roles within the gut microbiota and offer a foundation for further experimental investigations. As probiotic applications continue to expand, this study advances our knowledge of the genetic underpinnings that govern their functionality and highlights promising avenues for future therapeutic interventions and personalized health strategies.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.2174/0113892029319746240812051356
Darya Egorova, Bjorn Olsson, Tatyana Kir'yanova, Elena Plotnikova
Background: Hydroxylated biphenyls are currently recognized as secondary pollutants that are hazardous to animals and humans. Bacterial degradation is the most effective method for the degradation of hydroxylated biphenyls. Several strains capable of degrading polychlorinated biphenyls have been described, which also degrade hydroxylated biphenyls. Objectives: 1) To study the biodegradative properties of the Rhodococcus opacus strain KT112-7 towards mono-hydroxylated biphenyls. 2) To analyze the genome of the Rhodococcus opacus strain KT112-7. 3) To identify the genetic basis for the unique biodegradative potential of the Rhodococcus opacus strain KT112-7. Methods: A genome analysis of the strain KT112-7 was conducted based on whole-genome sequencing using various programs and databases (Velvet, CONTIGuator, RAST, KEGG) for annotation and identification of protein-coding sequences. The strain KT112-7 was cultivated in a K1 mineral medium supplemented with mono-hydroxy biphenyls or mono-hydroxybenzoic acids as the carbon source. For the growth test mono-hydroxybiphenyls or mono-hydroxybenzoic acids were dosed at concentrations of 0.5 g/L and 1.0 g/L correspondently, and the bacterial growth was monitored by the optical density. For the biodegradative activity test, mono-hydroxybiphenyls were dosed at a concentration of 0.1 g/L in vials, inoculated with late exponential phase bacteria previously acclimated on biphenyl. Compound analysis was performed using GC-MS, HPLC, and spectrophotometry. Results: It was found that the genome of strain KT112-7 consists of a chromosome and 2 plasmids. Biphenyl degradation genes (bph genes) were identified on plasmid PRHWK1 and the chromosome, as well as hydroxybenzoic acid degradation genes on the chromosome. The strain KT112-7 was shown to degrade mono-hydroxylated biphenyls to basal metabolic compounds of the cell, with the highest destructive activity observed towards 3- and 4-hydroxylated biphenyls (98%). Conclusion: The Rhodococcus opacus strain KT112-7 is characterized by genetic systems that contribute to its high biodegradative potential towards mono-hydroxylated biphenyls and their metabolites. Thus, the strain KT112-7 is promising for use in hydroxybiphenyl degradation technologies.
{"title":"An Assessment of the Degradation Potential and Genomic Insights Towards Hydroxylated Biphenyls by Rhodococcus opacus Strain KT112-7","authors":"Darya Egorova, Bjorn Olsson, Tatyana Kir'yanova, Elena Plotnikova","doi":"10.2174/0113892029319746240812051356","DOIUrl":"https://doi.org/10.2174/0113892029319746240812051356","url":null,"abstract":"Background: Hydroxylated biphenyls are currently recognized as secondary pollutants that are hazardous to animals and humans. Bacterial degradation is the most effective method for the degradation of hydroxylated biphenyls. Several strains capable of degrading polychlorinated biphenyls have been described, which also degrade hydroxylated biphenyls. Objectives: 1) To study the biodegradative properties of the Rhodococcus opacus strain KT112-7 towards mono-hydroxylated biphenyls. 2) To analyze the genome of the Rhodococcus opacus strain KT112-7. 3) To identify the genetic basis for the unique biodegradative potential of the Rhodococcus opacus strain KT112-7. Methods: A genome analysis of the strain KT112-7 was conducted based on whole-genome sequencing using various programs and databases (Velvet, CONTIGuator, RAST, KEGG) for annotation and identification of protein-coding sequences. The strain KT112-7 was cultivated in a K1 mineral medium supplemented with mono-hydroxy biphenyls or mono-hydroxybenzoic acids as the carbon source. For the growth test mono-hydroxybiphenyls or mono-hydroxybenzoic acids were dosed at concentrations of 0.5 g/L and 1.0 g/L correspondently, and the bacterial growth was monitored by the optical density. For the biodegradative activity test, mono-hydroxybiphenyls were dosed at a concentration of 0.1 g/L in vials, inoculated with late exponential phase bacteria previously acclimated on biphenyl. Compound analysis was performed using GC-MS, HPLC, and spectrophotometry. Results: It was found that the genome of strain KT112-7 consists of a chromosome and 2 plasmids. Biphenyl degradation genes (bph genes) were identified on plasmid PRHWK1 and the chromosome, as well as hydroxybenzoic acid degradation genes on the chromosome. The strain KT112-7 was shown to degrade mono-hydroxylated biphenyls to basal metabolic compounds of the cell, with the highest destructive activity observed towards 3- and 4-hydroxylated biphenyls (98%). Conclusion: The Rhodococcus opacus strain KT112-7 is characterized by genetic systems that contribute to its high biodegradative potential towards mono-hydroxylated biphenyls and their metabolites. Thus, the strain KT112-7 is promising for use in hydroxybiphenyl degradation technologies.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.2174/0113892029319425240813074610
Fu Li, Xiaomei Yang, Xiuxiu Wang, Jiajia Mi, Xiao Mou, Li Song, Libo Zheng
Background: B-ALL is a hematologic malignancy that recurs in approximately 10-20% of children and has a poor prognosis. New prognostic biomarkers are needed to improve individualized therapy and achieve better clinical outcomes. Methods: In this study, high-throughput sequencing technology was used to detect the BCR and TCR repertoires in children with B-ALL. Results: We observed a gradual increase in the diversity of the BCR and TCR repertoires during the developmental stages (Pro-, Common-, Pre-B-ALL) of precursor B-ALL cells. Conversely, as minimal residual disease (MRD) levels on day 19 of induction therapy increased, the BCR/TCR repertoire diversity decreased. Furthermore, the BCR/TCR repertoire diversity was significantly greater in B-ALL patients at low risk and those harboring the ETV6/RUNX1 fusion than in patients with medium-risk disease and those harboring the ZNF384 fusion. Notably, the abundance of BCR/TCR clones varied significantly among patients with B-ALL and different clinical characteristics. Specifically, patients with Pre-B-ALL, low-risk disease, D19MRD levels <1%, and harboring the ETV6/RUNX1 fusion exhibited a predominance of BCR/TCR small clones. In our study, we noted an imbalanced occurrence of V and J gene utilization among patients with BALL; however, there seemed to be no discernible correlation with the clinical attributes. Conclusion: BCR/TCR repertoires are expected to be potential prognostic biomarkers for patients with B-ALL.
{"title":"High-Throughput Sequencing Revealing BCR and TCR Repertoires as Potential Prognostic Biomarkers for Pediatric Patients with B-ALL","authors":"Fu Li, Xiaomei Yang, Xiuxiu Wang, Jiajia Mi, Xiao Mou, Li Song, Libo Zheng","doi":"10.2174/0113892029319425240813074610","DOIUrl":"https://doi.org/10.2174/0113892029319425240813074610","url":null,"abstract":"Background: B-ALL is a hematologic malignancy that recurs in approximately 10-20% of children and has a poor prognosis. New prognostic biomarkers are needed to improve individualized therapy and achieve better clinical outcomes. Methods: In this study, high-throughput sequencing technology was used to detect the BCR and TCR repertoires in children with B-ALL. Results: We observed a gradual increase in the diversity of the BCR and TCR repertoires during the developmental stages (Pro-, Common-, Pre-B-ALL) of precursor B-ALL cells. Conversely, as minimal residual disease (MRD) levels on day 19 of induction therapy increased, the BCR/TCR repertoire diversity decreased. Furthermore, the BCR/TCR repertoire diversity was significantly greater in B-ALL patients at low risk and those harboring the ETV6/RUNX1 fusion than in patients with medium-risk disease and those harboring the ZNF384 fusion. Notably, the abundance of BCR/TCR clones varied significantly among patients with B-ALL and different clinical characteristics. Specifically, patients with Pre-B-ALL, low-risk disease, D19MRD levels <1%, and harboring the ETV6/RUNX1 fusion exhibited a predominance of BCR/TCR small clones. In our study, we noted an imbalanced occurrence of V and J gene utilization among patients with BALL; however, there seemed to be no discernible correlation with the clinical attributes. Conclusion: BCR/TCR repertoires are expected to be potential prognostic biomarkers for patients with B-ALL.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Biobanks are necessary resources for the storage and management of human biological materials, such as biofluids, tissues, cells, or nucleotides. They play a significant role in the development of new treatments and the advancement of basic and translational research, especially in the field of biomarkers discovery and validation. The regulatory landscape for biobanks, which is necessary to safeguard both privacy and scientific discoveries, exhibits significant heterogeneity across different countries and regions. This article outlines the standards that modern biobanks should fulfill in the European Union (EU), including general, structural, resource, process, and quality requirements. Special attention is given to the importance of transparency and donor consent following the General Data Protection Regulation (GDPR) and the ISO 20387:2018, the international standard specifies general requirements for biobanks. A dedicated section covers the preparation of donor information materials, emphasizing consent for research involvement and personal data processing. The delicate balance between donors' privacy rights and scientific research promotion is also discussed, with a focus on the patenting and economic use of biological material- derived inventions and data. Considering these factors, it would be warranted to refine legal frameworks and foster interdisciplinary collaboration to ethically and responsibly expand biobanking.
:生物库是储存和管理人类生物材料(如生物液体、组织、细胞或核苷酸)的必要资源。它们在开发新的治疗方法、推进基础研究和转化研究方面发挥着重要作用,尤其是在生物标志物的发现和验证领域。生物库是保护隐私和科学发现的必要条件,但不同国家和地区对生物库的监管存在很大差异。本文概述了欧盟(EU)现代生物库应达到的标准,包括一般、结构、资源、流程和质量要求。文章特别关注了《一般数据保护条例》(GDPR)和国际标准 ISO 20387:2018 规定的生物库一般要求中透明度和捐献者同意的重要性。其中专门有一节涉及捐赠者信息材料的准备,强调同意参与研究和个人数据处理。此外,还讨论了捐赠者隐私权与促进科学研究之间的微妙平衡,重点关注生物材料衍生发明和数据的专利申请和经济用途。考虑到这些因素,有必要完善法律框架,促进跨学科合作,以合乎伦理和负责任的方式扩大生物库。
{"title":"The Regulatory Landscape of Biobanks In Europe: From Accreditation to Intellectual Property","authors":"Antonella Corradi, Giuseppina Bonizzi, Elham Sajjadi, Francesca Pavan, Marzia Fumagalli, Luigi Orlando Molendini, Massimo Monturano, Cristina Cassi, Camilla Rosella Musico, Luca Leoni, Chiara Frascarelli, Oriana Pala, Elena Guerini-Rocco, Adriana Albini, Roberto Orecchia, Nicola Fusco","doi":"10.2174/0113892029313697240729091922","DOIUrl":"https://doi.org/10.2174/0113892029313697240729091922","url":null,"abstract":": Biobanks are necessary resources for the storage and management of human biological materials, such as biofluids, tissues, cells, or nucleotides. They play a significant role in the development of new treatments and the advancement of basic and translational research, especially in the field of biomarkers discovery and validation. The regulatory landscape for biobanks, which is necessary to safeguard both privacy and scientific discoveries, exhibits significant heterogeneity across different countries and regions. This article outlines the standards that modern biobanks should fulfill in the European Union (EU), including general, structural, resource, process, and quality requirements. Special attention is given to the importance of transparency and donor consent following the General Data Protection Regulation (GDPR) and the ISO 20387:2018, the international standard specifies general requirements for biobanks. A dedicated section covers the preparation of donor information materials, emphasizing consent for research involvement and personal data processing. The delicate balance between donors' privacy rights and scientific research promotion is also discussed, with a focus on the patenting and economic use of biological material- derived inventions and data. Considering these factors, it would be warranted to refine legal frameworks and foster interdisciplinary collaboration to ethically and responsibly expand biobanking.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.2174/0113892029308243240709073945
Indu Priya Gudivada, Krishna Chaitanya Amajala
Background: The damage in the liver and hepatocytes is where the primary liver cancer begins, and this is referred to as Hepatocellular Carcinoma (HCC). One of the best methods for detecting changes in gene expression of hepatocellular carcinoma is through bioinformatics approaches. Objective: This study aimed to identify potential drug target(s) hubs mediating HCC progression using computational approaches through gene expression and protein-protein interaction datasets. Methodology: Four datasets related to HCC were acquired from the GEO database, and Differentially Expressed Genes (DEGs) were identified. Using Evenn, the common genes were chosen. Using the Fun Rich tool, functional associations among the genes were identified. Further, protein-protein interaction networks were predicted using STRING, and hub genes were identified using Cytoscape. The selected hub genes were subjected to GEPIA and Shiny GO analysis for survival analysis and functional enrichment studies for the identified hub genes. The up-regulating genes were further studied for immunohistopathological studies using HPA to identify gene/protein expression in normal vs HCC conditions. Drug Bank and Drug Gene Interaction Database were employed to find the reported drug status and targets. Finally, STITCH was performed to identify the functional association between the drugs and the identified hub genes. Results: The GEO2R analysis for the considered datasets identified 735 upregulating and 284 downregulating DEGs. Functional gene associations were identified through the Fun Rich tool. Further, PPIN network analysis was performed using STRING. A comparative study was carried out between the experimental evidence and the other seven data evidence in STRING, revealing that most proteins in the network were involved in protein-protein interactions. Further, through Cytoscape plugins, the ranking of the genes was analyzed, and densely connected regions were identified, resulting in the selection of the top 20 hub genes involved in HCC pathogenesis. The identified hub genes were: KIF2C, CDK1, TPX2, CEP55, MELK, TTK, BUB1, NCAPG, ASPM, KIF11, CCNA2, HMMR, BUB1B, TOP2A, CENPF, KIF20A, NUSAP1, DLGAP5, PBK, and CCNB2. Further, GEPIA and Shiny GO analyses provided insights into survival ratios and functional enrichment studied for the hub genes. The HPA database studies further found that upregulating genes were involved in changes in protein expression in Normal vs HCC tissues. These findings indicated that hub genes were certainly involved in the progression of HCC. STITCH database studies uncovered that existing drug molecules, including sorafenib, regorafenib, cabozantinib, and lenvatinib, could be used as leads to identify novel drugs, and identified hub genes could also be considered as potential and promising drug targets as they are involved in the gene-chemical interaction networks. Conclusion: The present study involved various integrated bioinformatics approaches, analyzing gen
{"title":"Integrative Bioinformatics Analysis for Targeting Hub Genes in Hepatocellular Carcinoma Treatment","authors":"Indu Priya Gudivada, Krishna Chaitanya Amajala","doi":"10.2174/0113892029308243240709073945","DOIUrl":"https://doi.org/10.2174/0113892029308243240709073945","url":null,"abstract":"Background: The damage in the liver and hepatocytes is where the primary liver cancer begins, and this is referred to as Hepatocellular Carcinoma (HCC). One of the best methods for detecting changes in gene expression of hepatocellular carcinoma is through bioinformatics approaches. Objective: This study aimed to identify potential drug target(s) hubs mediating HCC progression using computational approaches through gene expression and protein-protein interaction datasets. Methodology: Four datasets related to HCC were acquired from the GEO database, and Differentially Expressed Genes (DEGs) were identified. Using Evenn, the common genes were chosen. Using the Fun Rich tool, functional associations among the genes were identified. Further, protein-protein interaction networks were predicted using STRING, and hub genes were identified using Cytoscape. The selected hub genes were subjected to GEPIA and Shiny GO analysis for survival analysis and functional enrichment studies for the identified hub genes. The up-regulating genes were further studied for immunohistopathological studies using HPA to identify gene/protein expression in normal vs HCC conditions. Drug Bank and Drug Gene Interaction Database were employed to find the reported drug status and targets. Finally, STITCH was performed to identify the functional association between the drugs and the identified hub genes. Results: The GEO2R analysis for the considered datasets identified 735 upregulating and 284 downregulating DEGs. Functional gene associations were identified through the Fun Rich tool. Further, PPIN network analysis was performed using STRING. A comparative study was carried out between the experimental evidence and the other seven data evidence in STRING, revealing that most proteins in the network were involved in protein-protein interactions. Further, through Cytoscape plugins, the ranking of the genes was analyzed, and densely connected regions were identified, resulting in the selection of the top 20 hub genes involved in HCC pathogenesis. The identified hub genes were: KIF2C, CDK1, TPX2, CEP55, MELK, TTK, BUB1, NCAPG, ASPM, KIF11, CCNA2, HMMR, BUB1B, TOP2A, CENPF, KIF20A, NUSAP1, DLGAP5, PBK, and CCNB2. Further, GEPIA and Shiny GO analyses provided insights into survival ratios and functional enrichment studied for the hub genes. The HPA database studies further found that upregulating genes were involved in changes in protein expression in Normal vs HCC tissues. These findings indicated that hub genes were certainly involved in the progression of HCC. STITCH database studies uncovered that existing drug molecules, including sorafenib, regorafenib, cabozantinib, and lenvatinib, could be used as leads to identify novel drugs, and identified hub genes could also be considered as potential and promising drug targets as they are involved in the gene-chemical interaction networks. Conclusion: The present study involved various integrated bioinformatics approaches, analyzing gen","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-11DOI: 10.2174/0113892029301969240708094053
Xuan Wang, Ming-Hong Feng, Shao-Bo Wang, Hong Shi
Introduction: Currently, macaques are used as animal models for human disease in biomedical research. There are two macaques species widely used as animal models, i.e., cynomolgus macaques and rhesus macaques. Method: These two primates distribute widely, and their natural habitats are different. Cynomolgus macaques distribute in tropical climates, while rhesus macaques mostly distribute in relatively cold environments, and cynomolgus macaques have a common frostbite problem during winter when they are transferred to cold environments. In order to explore the molecular mechanisms underlying the temperature adaptation in macaques, genetic analysis and natural selection tests were performed. Based on the analysis of heat shock protein genes, DNAJC22, DNAJC28, and HSF5 showed positive selection signals. To these 3 genes, the significantly differential expression had been confirmed between cynomolgus macaques and Chinese rhesus macaques. Molecular evolution analysis showed that mutations of DNAJC22, DNAJC28, and HSF5 in Chinese rhesus macaques could enable them to gain the ability to rapidly regulate body temperature. The heat shock proteins provided an important function for Chinese rhesus macaques, allowing them to adapt to a wide range of temperatures and spread widely. Results: The selection time that was estimated suggested that the cold adaptation of Chinese rhesus macaques coincided with the time that the modern human populations migrated northward from tropic regions to relatively cold regions, and the selection genes were similar. Conclusion: This study elucidated the evolutionary history of cynomolgus macaques and rhesus macaques from molecular adaptation. Furthermore, it provided an evolutionary perspective to reveal the different distribution and adaptation of macaques. Cynomolgus macaques is an ideal biomedical animal model to mimic human natural frostbite.
{"title":"Melocular Evolution on Cold Temperature Adaptation of Chinese Rhesus Macaques","authors":"Xuan Wang, Ming-Hong Feng, Shao-Bo Wang, Hong Shi","doi":"10.2174/0113892029301969240708094053","DOIUrl":"https://doi.org/10.2174/0113892029301969240708094053","url":null,"abstract":"Introduction: Currently, macaques are used as animal models for human disease in biomedical research. There are two macaques species widely used as animal models, i.e., cynomolgus macaques and rhesus macaques. Method: These two primates distribute widely, and their natural habitats are different. Cynomolgus macaques distribute in tropical climates, while rhesus macaques mostly distribute in relatively cold environments, and cynomolgus macaques have a common frostbite problem during winter when they are transferred to cold environments. In order to explore the molecular mechanisms underlying the temperature adaptation in macaques, genetic analysis and natural selection tests were performed. Based on the analysis of heat shock protein genes, DNAJC22, DNAJC28, and HSF5 showed positive selection signals. To these 3 genes, the significantly differential expression had been confirmed between cynomolgus macaques and Chinese rhesus macaques. Molecular evolution analysis showed that mutations of DNAJC22, DNAJC28, and HSF5 in Chinese rhesus macaques could enable them to gain the ability to rapidly regulate body temperature. The heat shock proteins provided an important function for Chinese rhesus macaques, allowing them to adapt to a wide range of temperatures and spread widely. Results: The selection time that was estimated suggested that the cold adaptation of Chinese rhesus macaques coincided with the time that the modern human populations migrated northward from tropic regions to relatively cold regions, and the selection genes were similar. Conclusion: This study elucidated the evolutionary history of cynomolgus macaques and rhesus macaques from molecular adaptation. Furthermore, it provided an evolutionary perspective to reveal the different distribution and adaptation of macaques. Cynomolgus macaques is an ideal biomedical animal model to mimic human natural frostbite.","PeriodicalId":10803,"journal":{"name":"Current Genomics","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141609437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}