Publications by authors named "Kejun Wang"

56 Publications

Genetic Diversity of MHC B-F/B-L Region in 21 Chicken Populations.

Front Genet 2021 13;12:710770. Epub 2021 Aug 13.

National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.

The chicken major histocompatibility complex (MHC) on chromosome 16 is the most polymorphic region across the whole genome, and also an ideal model for genetic diversity investigation. The MHC B-F/B-L region is 92 kb in length with high GC content consisting of 18 genes and one pseudogene (Blec4), which plays important roles in immune response. To evaluate polymorphism of the Chinese indigenous chickens as well as to analyze the effect of selection to genetic diversity, we used WaferGen platform to identify sequence variants of the B-F/B-L region in 21 chicken populations, including the Red Jungle Fowl (RJF), Cornish (CS), White Leghorns (WLs), 16 Chinese domestic breeds, and two well-known inbred lines 6 and 7. A total of 3,319 single nucleotide polymorphism (SNPs) and 181 INDELs in the B-F/B-L region were identified among 21 populations, of which 2,057 SNPs (62%) and 159 INDELs (88%) were novel. Most of the variants were within the intron and the flanking regions. The average variation density was 36 SNPs and 2 INDELs per kb, indicating dramatical high diversity of this region. Furthermore, was identified as the hypervariable genes with 67 SNPs per kb. Chinese domestic populations showed higher diversity than the WLs and CS. The indigenous breeds, Nandan Yao (NY), Xishuangbanna Game (XG), Gushi (GS), and Xiayan (XY) chickens, were the top four with the highest density of SNPs and INDELs. The highly inbred lines 6 and 7 have the lowest diversity, which might be resulted from a long-term intense selection for decades. Collectively, we refined the genetic map of chicken MHC B-F/B-L region, and illustrated genetic diversity of 21 chicken populations. Abundant genetic variants were identified, which not only strikingly expanded the current Ensembl SNP database, but also provided comprehensive data for researchers to further investigate association between variants in MHC and immune traits.
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http://dx.doi.org/10.3389/fgene.2021.710770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414643PMC
August 2021

Lefty A is involved in sunitinib resistance of renal cell carcinoma cells via regulation of IL-8.

Biol Chem 2021 Sep 9;402(10):1247-1256. Epub 2021 Aug 9.

Medical Imaging Center, Taihe Hospital, No.32 Renmin South Road, Shiyan 442000, Hubei Province, China.

Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. Sunitinib has been used as the standard of treatment for first-line RCC therapy. Understanding mechanisms of sunitinib resistance in RCC cell is important for clinical therapy and drug development. We established sunitinib resistant RCC cells by treating cells with increasing concentrations of sunitinib and named resistant cells as RCC/SR. Lefty A, an important embryonic morphogen, was increased in RCC/SR cells. Targeted inhibition of Lefty via its siRNAs restored the sensitivity of renal resistant cells to sunitinib treatment. It was due to that si-Lefty can decrease the expression of interleukin-8 (IL-8) in RCC/SR cells. Knockdown of IL-8 abolished Lefty-regulated sunitinib sensitivity of RCC cells. Mechanistically, Lefty can regulate IL-8 transcription via activation of p65, one major transcription factor of IL-8. Collectively, our present revealed that Lefty A can regulate sunitinib sensitivity of RCC cells of via NF-κB/IL-8 signals. It indicated that targeted inhibition of Lefty might be a potent approach to overcome sunitinib resistance of RCC.
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http://dx.doi.org/10.1515/hsz-2021-0280DOI Listing
September 2021

The chicken pan-genome reveals gene content variation and a promoter region deletion in IGF2BP1 affecting body size.

Mol Biol Evol 2021 Jul 30. Epub 2021 Jul 30.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou 450046, China.

Domestication and breeding have reshaped the genomic architecture of chicken, but the retention and loss of genomic elements during these evolutionary processes remain unclear. We present the first chicken pan-genome constructed using 664 individuals, which identified an additional ∼66.5 Mb sequences that are absent from the reference genome (GRCg6a). The constructed pan-genome encoded 20,491 predicated protein-coding genes, of which higher expression level are observed in conserved genes relative to dispensable genes. Presence/absence variation (PAV) analyses demonstrated that gene PAV in chicken was shaped by selection, genetic drift, and hybridization. PAV-based GWAS identified numerous candidate mutations related to growth, carcass composition, meat quality, or physiological traits. Among them, a deletion in the promoter region of IGF2BP1 affecting chicken body size is reported, which is supported by functional studies and extra samples. This is the first time to report the causal variant of chicken body size QTL located at chromosome 27 which was repeatedly reported. Therefore, the chicken pan-genome is a useful resource for biological discovery and breeding. It improves our understanding of chicken genome diversity and provides materials to unveil the evolution history of chicken domestication.
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http://dx.doi.org/10.1093/molbev/msab231DOI Listing
July 2021

Genomic Analysis Reveals Human-Mediated Introgression From European Commercial Pigs to Henan Indigenous Pigs.

Front Genet 2021 18;12:705803. Epub 2021 Jun 18.

College of Animal Sciences and Technology, Henan Agricultural University, Zhengzhou, China.

Introgression of genetic features from European pigs into Chinese pigs was reported possibly contributing to improvements in productivity traits, such as feed conversion efficiency and body size. However, the genomic differences from European pigs and the potential role of introgression in Henan indigenous pigs remains unclear. In this study, we found significant introgression from European pigs into the genome of Chinese indigenous pigs, especially in Henan indigenous pigs. The introgression in Henan indigenous pigs, particularly in the Nanyang black pig, was mainly derived from Duroc pigs. Most importantly, we found that the , and genes were introgressed and reshaped by artificial selection, and these may have contributed to increases in pig body size and feed conversion efficiency. Our results suggest that human-mediated introgression and selection have reshaped the genome of Henan pigs and improved several of their desired traits. These findings contribute to our understanding of the history of Henan indigenous pigs and provide insights into the genetic mechanisms affecting economically important traits in pig populations.
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http://dx.doi.org/10.3389/fgene.2021.705803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249855PMC
June 2021

Underwater Acoustic Target Recognition Based on Depthwise Separable Convolution Neural Networks.

Sensors (Basel) 2021 Feb 18;21(4). Epub 2021 Feb 18.

College of Automation, Harbin Engineering University, Harbin 150001, China.

Facing the complex marine environment, it is extremely challenging to conduct underwater acoustic target feature extraction and recognition using ship-radiated noise. In this paper, firstly, taking the one-dimensional time-domain raw signal of the ship as the input of the model, a new deep neural network model for underwater target recognition is proposed. Depthwise separable convolution and time-dilated convolution are used for passive underwater acoustic target recognition for the first time. The proposed model realizes automatic feature extraction from the raw data of ship radiated noise and temporal attention in the process of underwater target recognition. Secondly, the measured data are used to evaluate the model, and cluster analysis and visualization analysis are performed based on the features extracted from the model. The results show that the features extracted from the model have good characteristics of intra-class aggregation and inter-class separation. Furthermore, the cross-folding model is used to verify that there is no overfitting in the model, which improves the generalization ability of the model. Finally, the model is compared with traditional underwater acoustic target recognition, and its accuracy is significantly improved by 6.8%.
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http://dx.doi.org/10.3390/s21041429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922821PMC
February 2021

Detection Line Spectrum of Ship Radiated Noise Based on a New 3D Chaotic System.

Sensors (Basel) 2021 Feb 25;21(5). Epub 2021 Feb 25.

College of Automation, Harbin Engineering University, Harbin 150001, China.

This paper proposes a new detection model of a weak signal based on a third-order chaotic system. Using a dynamic analysis tool, such as the Lyapunov exponent and the bifurcation diagram, variations of dynamic behavior can be observed, and the weak signal underwater can be picked up. In order to improve the observability of detection signals in the time domain and frequency domain, the spectral entropy complexity algorithm (SE) and complexity algorithms are used to analyze and extract the weak signal. The experimental results show that the spectrum extraction based on the complexity algorithm can accurately reflect the dynamic characteristics of the detected signal. It provides the theoretical direction and experimental data support for the application of the chaotic system in the field of acoustic detection.
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http://dx.doi.org/10.3390/s21051610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956339PMC
February 2021

Mitochondrial Fusion Potentially Regulates a Metabolic Change in Tibetan Chicken Embryonic Brain During Hypoxia.

Front Cell Dev Biol 2021 9;9:585166. Epub 2021 Feb 9.

Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.

The Tibetan chickens (; TBCs) are an indigenous breed found in the Qinghai-Tibet Plateau that are well-adapted to a hypoxic environment. As of now, energy metabolism of the TBCs embryonic brain has been little examined. This study investigated changes in energy metabolism in TBCs during hypoxia, and compared energy metabolism in TBCs and Dwarf Laying Chickens (DLCs), a lowland chicken breed, to explore underlying mechanisms of hypoxia adaptation. We found TBCs exhibited decreased oxygen consumption rates (OCR) and ATP levels as well as an increased extracellular acidification rate (ECAR) during hypoxia. Nevertheless, OCR/ECAR ratios indicated aerobic metabolism still dominated under hypoxia. Most important, our results revealed significant differences in TBCs brain cellular metabolism compared to DLCs under hypoxia. Compared to DLCs, TBCs had higher OCR and TCA cycle activities during hypoxia. Also, TBCs had more mitochondrial content, increased mitochondrial aspect ratio and MFN1, MFN2, and OPA1 proteins which have previously been reported to control mitochondrial fusion were expressed at higher levels in TBCs compared to DLCs, suggesting that TBCs may regulate energy metabolism by increasing the level of mitochondrial fusion. In summary, TBCs can reduce aerobic metabolism and increase glycolysis to enable adaptation to hypoxia. Regulation of mitochondrial fusion via MFN1, MFN2, and OPA1 potentially enhances the ability of TBCs to survive on the Qinghai-Tibet Plateau.
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http://dx.doi.org/10.3389/fcell.2021.585166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900496PMC
February 2021

Characterization and comparison of the bacterial community between complete intensive and extensive feeding patterns in pigs.

AMB Express 2021 Feb 25;11(1):32. Epub 2021 Feb 25.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, China.

To investigate and compare the gut microbiota structures in complete intensive feeding pattern (CP) and extensive feeding pattern (EP) groups, a total of 20 pigs were divided into two groups and fed the same diet. The fecal microbial composition was profiled using 16S rRNA gene sequencing. Our results showed that seventeen predominant genera were present in each pig sample and constituted the phylogenetic core of the microbiota at the class level. The abundance of most of the core microbial flora were significantly higher in the CP group than in the EP group (P < 0.05), while the abundance of Gammaproteobacteria was significantly lower in the CP group than in the EP group (P < 0.05). The CP group had significantly greater community diversity, richness, and evenness than the EP group (P < 0.05). Functional prediction analysis indicated that intestinal microbial species potentially led to faster growth and an increased fat accumulation capacity in the CP group; however, disease resistance was weaker in the CP group than in the EP group. In conclusion, EP pigs have a wider range of activity and better animal welfare than CP pigs, which helps reduce the occurrence of diseases and neurological symptoms. To explore the effect of intestinal flora on disease resistance in pigs at the molecular level, Coprococcus, which is a key gut bacterium in the intestine, was selected for isolation and purification and cocultured with intestinal epithelial cells. qPCR was performed to determine the effect of Coprococcus on SLA-DRB gene expression in intestinal epithelial cells. The results showed that Coprococcus enhanced SLA-DRB gene expression in intestinal epithelial cells. The results provide useful reference data for further study on the relationship between intestinal flora and pig disease resistance.
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http://dx.doi.org/10.1186/s13568-021-01191-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907295PMC
February 2021

Integrated analysis of transcriptomic and proteomic analyses reveals different metabolic patterns in the livers of Tibetan and Yorkshire pigs.

Anim Biosci 2021 May 13;34(5):922-930. Epub 2020 Oct 13.

College of Animal Science, Tibet Agriculture and Animal Husbandry University, Linzhi, Xizang 86000, China.

Objective: Tibetan pigs, predominantly originating from the Tibetan Plateau, have been subjected to long-term natural selection in an extreme environment. To characterize the metabolic adaptations to hypoxic conditions, transcriptomic and proteomic expression patterns in the livers of Tibetan and Yorkshire pigs were compared.

Methods: RNA and protein were extracted from liver tissue of Tibetan and Yorkshire pigs (n = 3, each). Differentially expressed genes and proteins were subjected to gene ontology and Kyoto encyclopedia of genes and genomes functional enrichment analyses.

Results: In the RNA-Seq and isobaric tags for relative and absolute quantitation analyses, a total of 18,791 genes and 3,390 proteins were detected and compared. Of these, 273 and 257 differentially expressed genes and proteins were identified. Evidence from functional enrichment analysis showed that many genes were involved in metabolic processes. The combined transcriptomic and proteomic analyses revealed that small molecular biosynthesis, metabolic processes, and organic hydroxyl compound metabolic processes were the major processes operating differently in the two breeds. The important genes include retinol dehydrogenase 16, adenine phosphoribosyltransferase, prenylcysteine oxidase 1, sorbin and SH3 domain containing 2, ENSSSCG00000036224, perilipin 2, ladinin 1, kynurenine aminotransferase 1, and dimethylarginine dimethylaminohydrolase 1.

Conclusion: The findings of this study provide novel insight into the high-altitude metabolic adaptation of Tibetan pigs.
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http://dx.doi.org/10.5713/ajas.20.0342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100475PMC
May 2021

Identification of microflora related to growth performance in pigs based on 16S rRNA sequence analyses.

AMB Express 2020 Oct 29;10(1):192. Epub 2020 Oct 29.

College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, 450046, China.

Intestinal microorganisms have been shown to be important factors affecting the growth performance of pigs. Therefore, to investigate the effect of the intestinal microflora structure on the growth performance of pigs, samples from Duroc (n = 10), Landrace (n = 9) and Yorkshire (n = 21) pigs under the same diet and feeding conditions were collected. The fecal microbial composition was profiled via 16S ribosomal RNA (rRNA) gene sequencing. We also analyzed their growth performance. We found that Duroc and Landrace pigs had significant differences in average daily gain (ADG), feed efficiency ratio (FER), growth index (GI), and number of days taken to reach 100 kg (P < 0.05). Moreover, through analysis of the intestinal flora, we also identified 18 species of intestinal flora with significant differences between Duroc and Landrace pigs (P < 0.05). To eliminate the influence of genetic background, the differential intestinal flora of 21 Yorkshire pigs with differences in growth performance was analyzed. The results showed that there were significant correlations between Barnesiella, Dorea, Clostridium and Lactobacillus and pig growth performance. To explore the effect of the intestinal flora on the growth performance of pigs at the molecular level, Lactobacillus, which is the most abundant in the intestine, was selected for isolation and purification and cocultured with intestinal epithelial cells. qPCR was used to determine the effect of Lactobacillus on MC4R gene expression in intestinal epithelial cells. The results showed that Lactobacillus inhibited MC4R gene expression in these cells. The results provide a useful reference for further study of the relationship between the intestinal flora and pig growth performance.
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http://dx.doi.org/10.1186/s13568-020-01130-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596147PMC
October 2020

Population Genetic Analysis of Ten Geographically Isolated Tibetan Pig Populations.

Animals (Basel) 2020 Jul 29;10(8). Epub 2020 Jul 29.

Animal Science College, Tibet Agriculture and Animal Husbandry University, Linzhi 860000, China.

Several geographically isolated populations of Tibetan pigs inhabit the high-altitude environment of the Tibetan Plateau. Their genetic relationships, contribution to the pool of genetic diversity, and their origin of domestication are unclear. In this study, whole-genome re-sequencing data from 10 geographically isolated Tibetan pig populations were collected and analyzed. Population genetic analyses revealed limited genetic differentiation among the Tibetan pig populations. Evidence from deleterious variant analysis indicated that population-specific deleterious variants were the major component of all mutational loci. Contribution to the meta-population was largest in the TT (Qinghai-Tibet Plateau) population, based on gene diversity or allelic diversity. Selective sweep analysis revealed numerous genes, including RXFP1, FZD1, OR1F1, TBX19, MSTN, ESR1, MC1R, HIF3A, and EGLN2 which are involved in lung development, hard palate development, coat color, hormone metabolism, facial appearance, and perception of smell. These findings increase our understanding of the origins and domestication of the Tibetan pig, and help optimize the strategy for their conservation.
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http://dx.doi.org/10.3390/ani10081297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460208PMC
July 2020

4D Printing Strain Self-Sensing and Temperature Self-Sensing Integrated Sensor-Actuator with Bioinspired Gradient Gaps.

Adv Sci (Weinh) 2020 Jul 13;7(13):2000584. Epub 2020 May 13.

State Key Laboratory of Material Processing and Die & Mould Technology Huazhong University of Science and Technology Wuhan Hubei 430074 China.

Integrated sensor-actuators with exciting functionalities, such as action self-sensing, position self-sensing, posture self-sensing, or active sensing, are promising for applications in biomedical device, human-machine interaction, intelligent self-protection devices, and humanoid robots. Despite recent progress, it remains challenging to achieve a macroscopical integrated sensor-actuator in a material system with microstructures. To address this critical challenge, a 4D printing bioinspired microstructure strategy is reported to design a high-performance integrated sensor-actuator capable of simultaneous actuation and sensation. Decoupled thermal stimulation and strain sensation is achieved by combining nanocarbon black/polylactic acid composites with bioinspired gradient microgap structures. As a result, printed integrated sensor-actuators can actively touch objects triggered by thermal stimulation and self-sense the touching state through the resistance change. It is anticipated that the basic design principle underlying this behavior can be used to develop integrated sensor-actuators of various shapes and functionalities to meet desirable applications.
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http://dx.doi.org/10.1002/advs.202000584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341108PMC
July 2020

Bacterial magnetic particles-polyethylenimine vectors deliver target genes into multiple cell types with a high efficiency and low toxicity.

Appl Microbiol Biotechnol 2020 Aug 16;104(15):6799-6812. Epub 2020 Jun 16.

Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing, 100193, China.

Bacterial magnetic particles (BMPs) are biosynthesized magnetic nano-scale materials with excellent dispersibility and biomembrane enclosure properties. In this study, we demonstrate that BMPs augment the ability of polyethylenimine (PEI) to deliver target DNA into difficult-to-transfect primary porcine liver cells, with transfection efficiency reaching over 30%. Compared with standard lipofection and polyfection, BMP-PEI gene vectors significantly enhanced the transfection efficiencies for the primary porcine liver cells and C2C12 mouse myoblast cell lines. To better understand the mechanism of magnetofection using BMP-PEI/DNA vectors, transmission electron microscopy (TEM) images of transfected Cos-7, HeLa, and HEP-G2 cells were observed. We found that the BMP-PEI/DNA complexes were trafficked into the cytoplasm and nucleus by way of vesicular transport and endocytosis. Our study builds support for the versatile BMP-PEI vector transfection system, which might be exploited to transfect a wide range of cell types or even to reach specific targets in the treatment of disease. KEY POINTS: • We constructed a BMP-PEI gene delivery vector by combining BMPs and PEI. • The vector significantly enhanced transfection efficiencies in eukaryotic cell lines. • The transfection mechanism of this vector was explained in our study.
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http://dx.doi.org/10.1007/s00253-020-10729-2DOI Listing
August 2020

Genome-Wide Analysis Reveals Human-Mediated Introgression from Western Pigs to Indigenous Chinese Breeds.

Genes (Basel) 2020 03 4;11(3). Epub 2020 Mar 4.

National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, Beijing key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, Department of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.

Genetic variations introduced via introgression from Western to Chinese pigs have contributed to the performance of Chinese breeds in traits such as growth rate and feed conversion efficiency. However, little is known about the underlying genomic changes that occurred during introgression and the types of traits affected by introgression. To address these questions, 525 animals were characterized using an SNP array to detect genomic regions that had been introgressed from European to indigenous Chinese breeds. The functions of genes located in introgressed regions were also investigated. Our data show that five out of six indigenous Chinese breeds show evidence of introgression from Western pigs, and eight introgressed genome regions are shared by five of the Chinese breeds. A region located on chr13: 12.8-13.1 M was affected by both introgression and artificial selection, and this region contains the glucose absorption related gene, , and the sensory related gene, . The results provide a foundation for understanding introgression from Western to indigenous Chinese pigs.
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http://dx.doi.org/10.3390/genes11030275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140852PMC
March 2020

Integrated Analysis of miRNA-mRNA Network Reveals Different Regulatory Patterns in the Endometrium of Meishan and Duroc Sows during Mid-Late Gestation.

Animals (Basel) 2020 Mar 3;10(3). Epub 2020 Mar 3.

Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Embryo loss is a major factor affecting profitability in the pig industry. Embryonic mortality occurs during peri-implantation and mid-late gestation in pigs. Previous investigations have shown that the embryo loss rate in Meishan pigs is significantly lower than in commercial breeds. Most studies have focused on embryonic mortality during early gestation, but little is known about losses during mid-late gestation. In this study, we performed a transcriptome analysis of endometrial tissue in mid-late gestation sows (gestation days 49 and 72) sampled from two breeds (Meishan (MS) and Duroc (DU)) that have different embryo loss rates. We identified 411, 1113, 697, and 327 differentially expressed genes, and 14, 36, 57, and 43 differentially expressed miRNAs in four comparisons (DU49 vs. DU72, DU49 vs. MS49, DU72 vs. MS72, and MS49 vs. MS72), respectively. Subsequently; seven differentially expressed mRNAs and miRNAs were validated using qPCR. Functional analysis suggested the differentially expressed genes and miRNAs target genes mainly involved in regulation of hormone levels, blood vessel development, developmental process involved in reproduction, embryonic placenta development, and the immune system. A network analysis of potential miRNA-gene interactions revealed that differentially expressed miRNAs in Meishan pigs are involved in the response to estradiol and oxygen levels, and affect angiogenesis and blood vessel development. The binding site on ssc-miR-503 for epidermal growth factor () and the binding site on ssc-miR-671-5p for estrogen receptor α (ESR1) were identified using a dual luciferase assay. The results of this study will enable further exploration of miRNA-mRNA interactions important in pig pregnancy and will help to uncover molecular mechanisms affecting embryonic mortality in pigs during mid-late gestation.
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http://dx.doi.org/10.3390/ani10030420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143271PMC
March 2020

Protein expression profiles in Meishan and Duroc sows during mid-gestation reveal differences affecting uterine capacity, endometrial receptivity, and the maternal-fetal Interface.

BMC Genomics 2019 Dec 17;20(1):991. Epub 2019 Dec 17.

Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, Beijing key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People's Republic of China.

Background: Embryonic mortality is a major concern in the commercial swine industry and primarily occurs early in gestation, but also during mid-gestation (~ days 50-70). Previous reports demonstrated that the embryonic loss rate was significant lower in Meishan than in commercial breeds (including Duroc). Most studies have focused on embryonic mortality in early gestation, but little is known about embryonic loss during mid-gestation.

Results: In this study, protein expression patterns in endometrial tissue from Meishan and Duroc sows were examined during mid-gestation. A total of 2170 proteins were identified in both breeds. After statistical analysis, 70 and 114 differentially expressed proteins (DEPs) were identified in Meishan and Duroc sows, respectively. Between Meishan and Duroc sows, 114 DEPs were detected at day 49, and 98 DEPs were detected at day 72. Functional enrichment analysis revealed differences in protein expression patterns in the two breeds. Around half of DEPs were more highly expressed in Duroc at day 49 (DUD49), relative to DUD72 and Meishan at day 49 (MSD49). Many DEPs appear to be involved in metabolic process such as arginine metabolism. Our results suggest that the differences in expression affect uterine capacity, endometrial matrix remodeling, and maternal-embryo cross-talk, and may be major factors influencing the differences in embryonic loss between Meishan and Duroc sows during mid-gestation.

Conclusions: Our data showed differential protein expression pattern in endometrium between Meishan and Duroc sows and provides insight into the development process of endometrium. These findings could help us further uncover the molecular mechanism involved in prolificacy.
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http://dx.doi.org/10.1186/s12864-019-6353-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918595PMC
December 2019

Multiomics-Based Colorectal Cancer Molecular Subtyping Using Local Scaling Network Fusion.

J Comput Biol 2020 08 4;27(8):1295-1302. Epub 2019 Dec 4.

Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

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http://dx.doi.org/10.1089/cmb.2019.0252DOI Listing
August 2020

Cinobufagin Induces Cell Cycle Arrest at the G2/M Phase and Promotes Apoptosis in Malignant Melanoma Cells.

Front Oncol 2019 4;9:853. Epub 2019 Sep 4.

Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, China.

Emerging evidence has shown that cinobufagin, as an active ingredient of Venenum Bufonis, inhibits tumor development. The aim of this study was to investigate the inhibitory effects of cinobufagin on A375 human malignant melanoma cells. MTT and colony formation assays showed that cinobufagin significantly inhibited A375 cell proliferation and cell colony formation. Additional studies demonstrated that cinobufagin markedly increased the levels of ATM serine/threonine kinase (ATM) and checkpoint kinase 2 (Chk2) and decreased the levels of cell division cycle 25C (CDC25C), cyclin-dependent kinase 1 (CDK1), and cyclin B, subsequently inducing G2/M cell cycle arrest in A375 cells. Moreover, cinobufagin clearly inhibited the levels of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), AKT, p-AKT, and B-cell lymphoma 2 (Bcl-2). By contrast, it increased the levels of Bcl-2-associated death promoter, Bcl-2-associated X, cytoplasmic cytochrome C, and apoptotic protease activating factor 1, leading to increased levels of cleaved caspase-9 and cleaved caspase-3, resulting in the apoptosis of A375 cells. Together, these results indicate that cinobufagin can induce cell cycle arrest at the G2/M phase and apoptosis, leading to inhibition of A375/B16 cell proliferation. Thus, cinobufagin may be useful for melanoma treatment.
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http://dx.doi.org/10.3389/fonc.2019.00853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738445PMC
September 2019

RRAS2 knockdown suppresses osteosarcoma progression by inactivating the MEK/ERK signaling pathway.

Authors:
Kejun Wang Kan Peng

Anticancer Drugs 2019 10;30(9):933-939

Department of Trauma Orthopaedics, West China Hospital of Sichuan University, Chengdu, People's Republic of China.

Aberrant function of RRAS2 drives malignant transformation in a various of cancers. However, little information exists on the function of RRAS2 in tumorigenesis of osteosarcoma. In this study, we investigated the effect of RRAS2 on osteosarcoma progression and its underlying mechanism. The gene expression level and prognostic power of RRAS2 in osteosarcoma were first investigated using the data from the Gene Expression Omnibus database. Then RNA interference was performed to silence the expression of RRAS2 in osteosarcoma cells. Quantitative real-time-PCR and western blot were used to examine the gene and protein expressions of RRAS2 in osteosarcoma cells. In-vitro cancer proliferation and migration were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide solution and wound-healing assays, respectively. We found that RRAS2 was significantly upregulated in osteosarcoma cells and high expression of RRAS2 was associated with a poor prognosis for patients with osteosarcoma. RNA interference decreased the gene and protein expression of RRAS2, reduced in-vitro the proliferation and migration of osteosarcoma cells, and suppressed the activation of the MEK/ERK signaling pathway. RRAS2 as an adverse prognostic factor promoted cell proliferation and migration by activating the MEK/ERK signaling pathway, and may provide new therapeutic value for osteosarcoma.
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http://dx.doi.org/10.1097/CAD.0000000000000799DOI Listing
October 2019

Comparative adipose transcriptome analysis digs out genes related to fat deposition in two pig breeds.

Sci Rep 2019 09 9;9(1):12925. Epub 2019 Sep 9.

Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

Fatness traits are important in pigs because of their implications for fattening efficiency, meat quality, reproductive performance and immunity. Songliao black pigs and Landrace pigs show important differences in production and meat quality traits, including fatness and muscle growth. Therefore, we used a high-throughput massively parallel RNA-seq approach to identify genes differentially expressed in backfat tissue between these two breeds (six pigs in each). An average of 37.87 million reads were obtained from the 12 samples. After statistical analysis of gene expression data by edgeR, a total of 877 differentially expressed genes were detected between the two pig breeds, 205 with higher expression and 672 with lower expression in Songliao pigs. Candidate genes (LCN2, CES3, DGKB, OLR1, LEP, PGM1, PCK1, ACACB, FADS1, FADS2, MOGAT2, SREBF1, PPARGC1B) with known effects on fatness traits were included among the DEGs. A total of 1071 lncRNAs were identified, and 85 of these lncRNAs were differentially expressed, including 53 up-regulated and 32 down-regulated lncRNAs, respectively. The differentially expressed genes and lncRNAs involved in glucagon signaling pathway, glycolysis/gluconeogenesis, insulin signaling pathway, MAPK signaling pathway and so on. Integrated analysis potential trans-regulating or cis-regulating relation between DEGs and DE lncRNAs, suggested lncRNA MSTRG.2479.1 might regulate the expressed level of VLDLR affecting porcine fat metabolism. These results provide a number of candidate genes and lncRNAs potentially involved in porcine fat deposition and provide a basis for future research on the molecular mechanisms underlying in fat deposition.
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http://dx.doi.org/10.1038/s41598-019-49548-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733950PMC
September 2019

A double-labeling marker-based method for estimating inbreeding and parental genomic components in a population under conservation.

Asian-Australas J Anim Sci 2020 Jan 1;33(1):12-23. Epub 2019 Jul 1.

College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

Objective: The objective of a conservation program is to maintain maximum genetic diversity and preserve the viability of a breed. However, the efficiency of a program is influenced by the ability to accurately measure and predict genetic diversity.

Methods: To examine this question, we conducted a simulation in which common measures (i.e. heterozygosity) and novel measures (identity-by-descent probabilities and parental genomic components) were used to estimate genetic diversity within a conserved population using double-labeled single nucleotide polymorphism markers.

Results: The results showed that the accuracy and sensitivity of identity-by-state probabilities and heterozygosity were close to identity by descent (IBD) probabilities, which reflect the true genetic diversity. Expected heterozygosity most closely aligned with IBD. All common measures suggested that practices used in the current Chinese pig conservation program result in a ~5% loss in genetic diversity every 10 generations. Parental genomic components were also analyzed to monitor real-time changes in genomic components for each male and female ancestor. The analysis showed that ~7.5% of male families and ~30% of female families were lost every 5 generations. After 50 generations of simulated conservation, 4 male families lost ~50% of their initial genomic components, and the genomic components for 24.8% of the female families were lost entirely.

Conclusion: In summary, compared with the true genetic diversity value obtained using double-labeled markers, expected heterozygosity appears to be the optimal indicator. Parental genomic components analysis provides a more detailed picture of genetic diversity and can be used to guide conservation management practices.
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http://dx.doi.org/10.5713/ajas.19.0035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946976PMC
January 2020

MicroRNA Sequencing Reveals the Effect of Different Levels of Non-Fibrous Carbohydrate/Neutral Detergent Fiber on Rumen Development in Calves.

Animals (Basel) 2019 Jul 28;9(8). Epub 2019 Jul 28.

College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China.

Rumen development in calves is affected by many factors, including dietary composition. MicroRNAs (miRNAs) are known to function in the development of the rumen in cattle, what is not known is how these miRNAs function in rumen development of calves fed with high and low ratios of non-fibrous carbohydrate (NFC)/neutral detergent fiber (NDF). A total of six healthy Charolais hybrids bull calves of similar weight were divided into two groups; three calves were fed a mixed diet with NFC/NDF = 1.35 (H group), and three were fed a mixed diet with NFC/NDF = 0.80 (L group). After 105 days on the diet, calves were sacrificed and rumen tissues were collected. Tissues were subjected to histological observation and miRNA expression analysis. Functional enrichment analysis was conducted on the target genes of the miRNAs. Targeting and regulatory relationships were verified by luciferase reporter assay and quantitative PCR (qPCR). We found that the length of rumen papilla in the L group was significantly greater than that in the H group, while the width of rumen papilla in H group was significantly greater than that that in L group. We identified 896 miRNAs; 540 known miRNAs, and 356 novel predicted miRNAs. After statistical testing, we identified 24 differentially expressed miRNAs (DEmiRNAs). miRNA-mRNA-cluster network analysis and literature reviews revealed that cell proliferation, differentiation, physical and nutrient stimuli processes participate in rumen development under different NFC/NDF levels. The regulatory relationships between three DEmiRNAs and five target genes were verified by examining the levels of expression. The binding sites on bta-miR-128 for the peroxisome proliferator activated receptor gamma () and solute carrier family 16 member 1 ( genes were investigated using a dual luciferase assay. The results of this study provide insight into the role of miRNAs in rumen development in calves under different NFC/NDF levels.
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http://dx.doi.org/10.3390/ani9080496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720277PMC
July 2019

Identification of lncRNAs and Genes Responsible for Fatness and Fatty Acid Composition Traits between the Tibetan and Yorkshire Pigs.

Int J Genomics 2019 2;2019:5070975. Epub 2019 Jun 2.

Animal Science College, Tibet Agriculture and Animal Husbandry University, Linzhi, Xizang, China.

Tibetan pigs from the Tibetan Plateau are characterized with a significant phenotypic difference relative to lowland pigs. In this study, a significant difference of the fatness and fatty acid composition traits was observed between the Tibetan and Yorkshire pigs. To uncover the involved mechanism, the expression profile of long noncoding RNAs (lncRNAs) and genes was compared between them. After serial filtered steps, 1,964 lncRNAs were obtained through our computational pipeline. In total, 63 and 715 lncRNAs and genes were identified to be differentially expressed. Evidence from and targeting analysis of lncRNAs demonstrated that some lncRNAs, such as and , played important roles in the fatness and fatty acid composition traits. Bioinformatics analysis revealed that many candidate genes were responsible for the two traits. Of these, , , , , , , , and were identified, which functioned in regulating the level of hexadecanoic acid, hexadecenoic acid, octadecenoic acid, and monounsaturated fatty acid. And , , , and were associated with the content of stearic acid, octadecadienoic acid, and polyunsaturated fatty acid. Candidate genes, which were responsible for fatness trait, consisted of , , , , , , , , , and . In addition, association analysis also revealed that 34 and 57 genes significantly correlated to the fatness and fatty acid composition trait, respectively. Working out the mechanism caused by these lncRNAs and candidate genes is proven to be complicated but is invaluable to our understanding of fatness and fatty acid composition traits.
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http://dx.doi.org/10.1155/2019/5070975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589220PMC
June 2019

Transcriptomic Analysis of Coding Genes and Non-Coding RNAs Reveals Complex Regulatory Networks Underlying the Black Back and White Belly Coat Phenotype in Chinese Wuzhishan Pigs.

Genes (Basel) 2019 03 7;10(3). Epub 2019 Mar 7.

Department of Animal Genetics and Breeding, National Engineering Laboratory for Animal Breeding, MOA Laboratory of Animal Genetics and Breeding, Beijing key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Coat color is one of the most important characteristics for distinguishing Chinese indigenous pig breeds. In Wuzhishan pigs, the animals have black on the back and white on the abdomen. However, the molecular genetic basis of this phenotype is unclear. In this study, we used high-throughput RNA sequencing to compare expression profiles of coding and non-coding RNAs from white and black skin samples obtained from individual Wuzhishan pigs. The expression profiling revealed that 194 lncRNAs (long non-coding RNAs), 189 mRNAs (messenger RNAs), and 162 miRNAs (microRNAs) had significantly different levels of expression (|log₂ fold change| > 1, -value < 0.05) in white and black skin. Compared to RNA levels in black skin, white skin had higher levels of expression of 185 lncRNAs, 181 mRNAs, and 23 miRNAs and lower levels of expression of 9 lncRNAs, 8 mRNAs, and 139 miRNAs. Functional analysis suggested that the differentially expressed transcripts are involved in biological processes such as melanin biosynthesis, pigmentation and tyrosine metabolism. Several key genes involved in melanogenesis, including , , , , , and had significantly different levels of expression in the two skin tissues. Potential lncRNA⁻miRNA⁻gene interactions were also examined. A total of 15 lncRNAs, 11 miRNAs and 7 genes formed 23 lncRNA⁻miRNA⁻gene pairs, suggesting that complex regulatory networks of coding and non-coding genes underlie the coat color trait in Wuzhishan pigs. Our study provides a foundation for understanding how lncRNA, miRNA and genes interact to regulate coat color in black-back/white-belly pigs. We also constructed lncRNA⁻miRNA⁻gene interaction networks to elucidate the complex molecular mechanisms underlying skin physiology and melanogenesis. The results extend our knowledge about the diversity of coat color among different domestic animals and provide a foundation for studying novel mechanisms that control coat color in Chinese indigenous pigs.
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http://dx.doi.org/10.3390/genes10030201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470719PMC
March 2019

Insights into the genetic diversity of indigenous goats and their conservation priorities.

Asian-Australas J Anim Sci 2019 10 9;32(10):1501-1510. Epub 2019 Feb 9.

National Center for Preservation and Utilization of Animal Genetic Resources, National Animal Husbandry Service, Beijing 100193, China.

Objective: An experiment was conducted to evaluate genetic diversity of 26 Chinese indigenous goats by 30 microsatellite markers, and then to define conservation priorities to set up the protection programs according to the weight given to within- and between-breed genetic diversity.

Methods: Twenty-six representative populations of Chinese indigenous goats, 1351 total, were sampled from different geographic regions of China. Within-breed genetic diversity and marker polymorphism were estimated calculating the mean number of alleles (MNA), observed heterozygosities (HO), expected heterozygosities (He), fixation index (FIS), effective number of alleles (NE) and allelic richness (Rt). Conservation priorities were analyzed by statistical methods.

Results: A relatively high level of genetic diversity was found in twenty-four populations, the exceptions were in the Daiyun and Fuqing goat populations. Within-breed kinship coefficients matrix identified seven highly inbred breeds which should be concerned. Of these, six breeds will get a negative contribution to heterozygosity when the method was based on proportional contribution to heterozygosity. Based on Weitzman or Piyasatian and Kinghorn methods, the breeds distant from others i.e. Inner Mongolia Cashmere goat, Chengdu Brown goat and Leizhou goat will obtain a high ranking. Evidence from Caballero and Toro and Fabuel et al. method prioritized Jining Gray goat, Liaoning Cashmere goat and Inner Mongolia Cashmere goat, that in agreement with results from Kinship-based methods.

Conclusion: Conservation priorities had planned according to multiple methods. Our results suggest Inner Mongolia Cashmere goat (most methods), Jining Gray goat and Liaoning Cashmere goat (high contribution to heterozygosity and total diversity) should be prioritized based on most methods. Furthermore, Daiyun goat and Shannan White goat also should be prioritized based on consideration of effective population size. However, if one breed could survive in changing conditions all the time, the straightforward approach is to increase its utilization and attraction for production via mining breed germplasm characteristic.
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http://dx.doi.org/10.5713/ajas.18.0737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718908PMC
October 2019

Whole-genome sequencing identifies potential candidate genes for reproductive traits in pigs.

Genomics 2020 01 30;112(1):199-206. Epub 2019 Jan 30.

College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, People's Republic of China. Electronic address:

Reproductive performance is a complex quantitative trait, that is determined by multiple genes, regulatory pathways and environmental factors. A list of major genes with large effect have been detected, although multiple QTLs are identified. To identify candidate genes for pig prolificacy, whole genome variants from five high- and five low-prolificacy Yorkshire sows were collected using whole-genome resequencing. A total of 13,955,609 SNPs and 2,666,366 indels were detected across the genome. Common differential SNPs and indels were identified between the two groups of sows. Genes encoding components of the TGF-beta signaling pathway were enriched with the variations, including BMP5, BMP6, BMP7, ACVR1, INHBA, ZFYVE9, TGFBR2, DCN, ID4, BAMBI, and ACVR2A. Several differential variants within these genes related to reproductive traits were identified to be associated with litter size. A comparison of selective regions and published QTL data suggests that NEDD9, SLC39A11, SNCA, and UNC5D are candidate genes for reproduction traits.
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http://dx.doi.org/10.1016/j.ygeno.2019.01.014DOI Listing
January 2020

Integrated miRNA and mRNA transcriptomes of spleen profiles between Yorkshire and Queshan black pigs.

Gene 2019 Mar 8;688:204-214. Epub 2018 Dec 8.

College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002), China. Electronic address:

Disease causes large economic losses to the pig industry worldwidely, immunity plays an important role in the process of resistance to disease. In the present study, to elucidate the molecular mechanisms underlying different levels of disease resistance, we obtained the miRNA and mRNA expression profiles from the spleens of three groups of sows, including 180-day-old Queshan Black (Q-F), 3-day-old Yorkshire (Y-N) and 180-day-old Yorkshire (Y-F) pigs. The results showed that 85 miRNAs and 5093 genes were differentially expressed in Y-F vs Y-N, and 20 miRNAs and 1283 genes were differentially expressed in Q-F vs Y-F. Gene ontology analysis of these differentially expressed genes revealed their critical roles in response to immune response-related signaling pathways. To investigate the molecular mechanisms underlying immune diversity based on differentially expressed miRNAs and genes, the regulatory network between the node miRNAs and genes were established using Cytoscape. The results showed that the identified candidate miRNAs and genes were associated with immune response, and also indicated their potential roles in disease resistance variance between different pig breeds and stages. From the above, this research detected the key factors that were involved in disease resistance, and provide useful information for disease resistance breeding.
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http://dx.doi.org/10.1016/j.gene.2018.11.077DOI Listing
March 2019

Research on the degradation of lightweight mirror surface accuracy.

Appl Opt 2018 Sep;57(27):7758-7763

The vibration test is one of many tests that space telescopes endure to ensure that functionality is not impaired by severe launch. Telescopes undergo detailed measurements, including mirror surface accuracy measurements. Due to the design shortcomings, degradation of lightweight mirror surface accuracy may exceed the design error budget at times. In this paper, we demonstrate a method to determine the cause of the degradation. By using inertia relief, the influence functions were obtained, and structural deformation was derived from finite element analysis. Based on the structural deformation, we found that the back frame of the telescope had insufficient torsional and bending stiffness. With the indicated need for higher stiffness, the rigidity of the back frame was improved. In addition, high- and low-temperature cycling was used to reduce residual stresses that cause high-frequency distortion. The new vibration test verified the mechanical safety and optical stability of the improved structure. The surface accuracy measured by an optical interferometer was maintained at 0.015 wave within the design error budget.
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http://dx.doi.org/10.1364/AO.57.007758DOI Listing
September 2018

Dissecting cancer heterogeneity based on dimension reduction of transcriptomic profiles using extreme learning machines.

PLoS One 2018 14;13(9):e0203824. Epub 2018 Sep 14.

Department of Biomedical Sciences, City University of Hong Kong, Hong Kong.

It is becoming increasingly clear that major malignancies such as breast, colorectal and gastric cancers are not single disease entities, but comprising multiple cancer subtypes of distinct molecular properties. Molecular subtyping has been widely used to dissect inter-tumor biological heterogeneity, in relation to clinical outcomes. A key step of this methodology is to perform unsupervised classification of gene expression profiles, which, however, often suffers challenges of high-dimensionality, feature redundancy as well as noise and irrelevant information. To overcome these limitations, we propose ELM-CC, which employs hidden observation features obtained from extreme learning machines (ELMs) for cancer classification. To demonstrate the effectiveness and usefulness, we applied ELM-CC for gastric and ovarian cancer subtyping. Comparing with the widely-used consensus clustering method, our approach demonstrated much better clustering performance and identified molecular subtypes that are much more clinically relevant.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203824PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138406PMC
March 2019
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