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Proteomics
Proteomics focuses on proteins—the executors of life activities that play a crucial role in organismal transcription regulation. It analyzes the composition, expression levels, and modification states of all dynamically changing proteins in tissues or cells, addressing the significant impact of proteome abundance dynamics on various life processes. Widely applied in medicine, agriculture, and animal husbandry. Qualitative Proteomics utilizes HPLC-MS/MS protein identification technology to identify samples including gel strips, IP, and CO-IP/Pull down samples. Quantitative Proteomics achieves accurate quantification and identification of all proteins expressed by a genome or in a complex mixed system. Current quantitative proteomics technologies are mainly categorized into labeled (TMT) and label-free (Label Free, DIA, PRM) approaches. BMKGENE provides multi-platform and multi-technology proteomics solutions.
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Metabolomics
Metabolomics, a downstream discipline of genomics, mainly targets small-molecule substances with a molecular weight of less than 1500 Da. It enables metabolites to reflect organisms’ responses to external stimuli and physiological/pathological changes more sensitively. Genetic variations-induced metabolite level changes are also within its research scope, providing a novel research perspective.
BMKGENE offers a full range of metabolomics services, including non-targeted metabolomics, widely targeted metabolomics, and targeted metabolomics. Using liquid chromatography-mass spectrometry (LC-MS) or gas chromatography-mass spectrometry (GC-MS), the dynamic changes in most small-molecule metabolites in organisms before and after external stimulation can be detected. The core of these services lies in identifying metabolites with significant differences between experimental and control groups and further exploring their correlation with physiological/pathological changes and the underlying mechanisms.
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Exosomal mRNA/LncRNA/CircRNA Sequencing-Illumina
Exosomes are small vesicles secreted by cells, typically ranging in diameter from 30 to 100 nanometers. These vesicles contain various RNA. Exosomes are believed to play crucial roles in intercellular communication, immune responses, and disease development, and can be disseminated to other parts of the body through bodily fluids such as plasma, saliva, and urine. They carry specific biomolecules to regulate the functions of recipient cells, influencing cellular physiological states. Exosomes are also considered to play key roles in disease development, including cancers, neurodegenerative diseases, and inflammatory conditions. Research on exosomes offers new insights and methods for the diagnosis, treatment, and prevention of diseases.
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Exosomal Small RNA Sequencing-Illumina
Exosomes are small vesicles secreted by cells, typically ranging in diameter from 30 to 100 nanometers. These vesicles contain various RNA. Among the RNA types in exosomes, the most common and extensively studied is microRNA (miRNA). miRNA is a class of non-coding small RNAs approximately 18-25 nucleotides in length. They mediate post-transcriptional gene silencing by binding to the 3′ untranslated region (3′ UTR) of target mRNAs, thereby regulating gene expression. For example, exosomes secreted by certain tumor cells contain specific miRNAs, such as miR-126 and miR-92a. These miRNAs can influence gene expression in recipient cells and promote tumor angiogenesis (Tomohiro Umezu, et al., Oncogene, 2012).
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BMKMANU S3000_Spatial Transcriptome
Spatial transcriptomics is a technique that allow us to capture and visualize gene expression within tissues. This can be crucial to understand how cells interact.
There are different platforms for this approach. On this matter, BMKGene has developed BMKManu 3000 Spatial transcriptome Chip, a platform that boost the technique performance, reaching subcellular resolution and enabling a multi-level resolution setting.
This chip encloses 4.2 million spots using a patented technology of microwells layered with beads loaded with spatially barcoded probes. With this method, after the capture and amplification, we obtain a cDNA library enriched with the barcoded samples that it’s Illumina compatible.
On the data, the combination of spatial barcode and UMIs ensures the accuracy and specificity of the data generated. Combining all the above, BMKManu provides an extremely versatile data setting.
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DNBSEQ pre-made libraries
DNBSEQ, developed by MGI, is an innovative NGS technology that has managed to decrease further down the sequencing costs and increase throughput. Preparation of DNBSEQ libraries involves DNA fragmentation, preparation of ssDNA, and rolling circle amplification to obtain the DNA nanoballs (DNB). These are then loaded onto a solid surface and subsequently sequenced by combinatorial Probe-Anchor Synthesis (cPAS). DNBSEQ technology combines the advantages of having a low amplification error rate with using high density error patterns with nanoballs, resulting in sequencing with higher throughput and accuracy.
Our pre-made library sequencing service enables customers to prepare Illumina sequencing libraries from diverse sources (mRNA, whole genome, amplicon, 10x libraries, among others), which are converted to MGI libraries in our laboratories to be sequenced in DNBSEQ-T7, enabling high data amounts at lower costs.
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Hi-C based Chromatin Interaction
Hi-C is a method designed to capture genomic configuration by combining probing proximity-based interactions and high-throughput sequencing. The method is based on chromatin crosslinking with formaldehyde, followed by digestion and re-ligation in a way that only fragments that are covalently linked will form ligation products. By sequencing these ligation products, it is possible to study the 3D organization of the genome. Hi-C enables studying the distribution of the portions of the genome that are lightly packed (A compartments, euchromatin) and more likely to be transcriptionally active, and the regions that are more tightly packed (B compartments, Heterochromatin). Hi-C can also be used to pinpoint Topologically Associated Domains (TADs), regions of the genome that have folded structures and are likely to have similar expression patterns, and to identify chromatin loops, DNA regions that are anchored together by proteins and that are often enriched in regulatory elements. BMKGene’s Hi-C sequencing service empowers researchers to explore the spatial dimensions of genomics, opening new avenues for understanding genome regulation and its implications in health and disease.
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PacBio 2+3 Full-Length mRNA Solution
While NGS-based mRNA sequencing is a versatile tool for quantifying gene expression, its reliance on short reads restricts its efficacy in complex transcriptomic analyses. On the other hand, PacBio sequencing (Iso-Seq) employs long-read technology, enabling the sequencing of full-length mRNA transcripts. This approach facilitates a comprehensive exploration of alternative splicing, gene fusions, and poly-adenylation, although it is not the primary choice for gene expression quantification. The 2+3 combination bridges the gap between Illumina and PacBio by relying on PacBio HiFi reads to identify the complete set of transcript isoforms and NGS sequencing to quantify the identical isoforms.
Platforms: PacBio Revio and Illumina NovaSeq
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Genome-wide Association Analysis
The aim of Genome-Wide Association Studies (GWAS) is to identify genetic variants (genotypes) linked to specific traits (phenotypes). By scrutinizing genetic markers across the entire genome in a large number of individuals, GWAS extrapolates genotype-phenotype associations through population-level statistical analyses. This methodology finds extensive applications in researching human diseases and exploring functional genes related to complex traits in animals or plants.
At BMKGENE, we offer two avenues for conducting GWAS on large populations: employing Whole-Genome Sequencing (WGS) or opting for a reduced representation genome sequencing method, the in-house-developed Specific-Locus Amplified Fragment (SLAF). While WGS suits smaller genomes, SLAF emerges as a cost-effective alternative for studying larger populations with longer genomes, effectively minimizing sequencing costs, while guaranteeing a high genetic marker discovery efficiency.
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Single- nuclei RNA Sequencing
The development of single-cell capture and custom library construction techniques, coupled with high-throughput sequencing, has revolutionized gene expression studies at the cell level. This breakthrough allows for deeper and more comprehensive analysis of complex cell populations, overcoming the limitations associated with averaging gene expression over all cells and preserving the true heterogeneity within these populations. While single-cell RNA sequencing (scRNA-seq) has undeniable advantages, it encounters challenges in certain tissues where the creation of a single-cell suspension proves difficult and requires fresh samples. At BMKGene, we address this hurdle by offering single-nucleus RNA sequencing (snRNA-seq) using the state-of-the-art 10X Genomics Chromium technology. This approach broadens the spectrum of samples amenable to transcriptome analysis at the single-cell level.
The isolation of nuclei is accomplished through the innovative 10X Genomics Chromium chip, featuring an eight-channel microfluidics system with double crossings. Within this system, gel beads incorporating barcodes, primers, enzymes, and a single nucleus are encapsulated in nanoliter-sized oil drops, forming Gel Bead-in-Emulsion (GEM). Following GEM formation, cell lysis and barcode release occur within each GEM. Subsequently, mRNA molecules undergo reverse transcription into cDNAs, incorporating 10X barcodes and Unique Molecular Identifiers (UMIs). These cDNAs are then subjected to standard sequencing library construction, facilitating a robust and comprehensive exploration of gene expression profiles at the single-cell level.
Platform: 10× Genomics Chromium and Illumina NovaSeq Platform
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Plant/Animal Whole Genome Sequencing
Whole Genome Sequencing (WGS) is technique used to determine the entirely of the DNA sequence of an organism’s genome at a single time.
Usually, the service is divided into two different groups depending on the existence of a reference genome:
- De novo whole genome sequencing. In this situation, the genome to be sequenced doesn’t have a reference genome available, and for that reason, the objective of this sequencing is to generate it (or to improve an existing one). This technique needs to use both, Illumina data and long-read sequencing to enhance the genome assembly by creating an overlap between reads.
- Re-sequencing. It refers to the whole genome sequencing of different individuals of species with known reference genomes. On this basis, the genomic differences of individuals or populations can be further identified.
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10x Genomics Visium Spatial Transcriptome
Spatial transcriptomics is a cutting-edge technology that allows researchers to investigate gene expression patterns within tissues while preserving their spatial context. One powerful platform in this domain is 10x Genomics Visium coupled with Illumina sequencing. The principle of 10X Visium lies on a specialized chip with a designated capture area where tissue sections are placed. This capture area contains barcoded spots, each corresponding to a unique spatial location within the tissue. The captured RNA molecules from the tissue are then labeled with unique molecular identifiers (UMIs) during the reverse transcription process. These barcoded spots and UMIs enable precise spatial mapping and quantification of gene expression at a single-cell resolution. The combination of spatially barcoded samples and UMIs ensures the accuracy and specificity of the data generated. By using this Spatial Transcriptomics technology, researchers can gain a deeper understanding of the spatial organization of cells and the complex molecular interactions occurring within tissues, offering invaluable insights into the mechanisms underlying biological processes in multiple fields, including oncology, neuroscience, developmental biology, immunology, and botanical studies.
Platform: 10X Genomics Visium and Illumina NovaSeq
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Full-Length mRNA Sequencing-Nanopore
While NGS-based mRNA sequencing is a versatile tool for quantifying gene expression, its reliance on short reads restricts its efficacy in complex transcriptomic analyses. On the other hand, nanopore sequencing employs long-read technology, enabling the sequencing of full-length mRNA transcripts. This approach facilitates a comprehensive exploration of alternative splicing, gene fusions, poly-adenylation, and the quantification of mRNA isoforms.
Nanopore sequencing, a method that relies on nanopore single-molecule real-time electrical signals, provides results in real-time. Guided by motor proteins, double-stranded DNA binds to nanopore proteins embedded in a biofilm, unwinding as it passes through the nanopore channel under a voltage difference. The distinctive electrical signals generated by different bases on the DNA strand are detected and classified in real-time, facilitating accurate and continuous nucleotide sequencing. This innovative approach overcomes short-read limitations and provides a dynamic platform for intricate genomic analysis, including complex transcriptomic studies, with immediate results.
Platform: Nanopore PromethION 48
