Integration of Cancer Gene Co-expression Network and Metabolic Network To Uncover Potential Cancer Drug Targets

Cell metabolism is critical for cancer cell transformation and progression. In this study, we have developed a novel method, named Met-express, that integrates a cancer gene co-expression network with the metabolic network to predict key enzyme-coding genes and metabolites in cancer cell metabolism. Met-express successfully identified a group of key enzyme-coding genes and metabolites in lung, leukemia, and breast cancers. Literature reviews suggest that approximately 33–53% of the predicted genes are either known or suggested anti-cancer drug targets, while 22% of the predicted metabolites are known or high-potential drug compounds in therapeutic use. Furthermore, experimental validations prove that 90% of the selected genes and 70% of metabolites demonstrate the significant anti-cancer phenotypes in cancer cells, implying that they may play important roles in cancer metabolism. Therefore, Met-express is a powerful tool for uncovering novel therapeutic biomarkers

Integration of Cancer Gene Co-expression Network and Metabolic Network To Uncover Potential Cancer Drug Targets

Cell metabolism is critical for cancer cell transformation and progression. In this study, we have developed a novel method, named Met-express, that integrates a cancer gene co-expression network with the metabolic network to predict key enzyme-coding genes and metabolites in cancer cell metabolism. Met-express successfully identified a group of key enzyme-coding genes and metabolites in lung, leukemia, and breast cancers. Literature reviews suggest that approximately 33–53% of the predicted genes are either known or suggested anti-cancer drug targets, while 22% of the predicted metabolites are known or high-potential drug compounds in therapeutic use. Furthermore, experimental validations prove that 90% of the selected genes and 70% of metabolites demonstrate the significant anti-cancer phenotypes in cancer cells, implying that they may play important roles in cancer metabolism. Therefore, Met-express is a powerful tool for uncovering novel therapeutic biomarkers

Integration of Cancer Gene Co-expression Network and Metabolic Network To Uncover Potential Cancer Drug Targets

Cell metabolism is critical for cancer cell transformation and progression. In this study, we have developed a novel method, named Met-express, that integrates a cancer gene co-expression network with the metabolic network to predict key enzyme-coding genes and metabolites in cancer cell metabolism. Met-express successfully identified a group of key enzyme-coding genes and metabolites in lung, leukemia, and breast cancers. Literature reviews suggest that approximately 33–53% of the predicted genes are either known or suggested anti-cancer drug targets, while 22% of the predicted metabolites are known or high-potential drug compounds in therapeutic use. Furthermore, experimental validations prove that 90% of the selected genes and 70% of metabolites demonstrate the significant anti-cancer phenotypes in cancer cells, implying that they may play important roles in cancer metabolism. Therefore, Met-express is a powerful tool for uncovering novel therapeutic biomarkers

Manufacture of esiRNA by means of a magnetic bead-integrated chip.

<p><b>A.</b> The schematic diagram shows the chip composed of a microwell array and magnetic beads coated with streptavidin. <b>B.</b> Large-scale manufacture of esiRNAs can be divided into three steps: target amplification and immobilization, transcription, and enzymatic digestion. <b>C.</b> Confirmation of PCR reactions using biotinylated or non-biotinylated primers. Amplification products (left), transcription products (middle), or esiRNA products (right) are detected only when biotinylated DNA primers are used. B: biotinylated primers.</p

Screen and validation of tyrosine kinase genes capable of regulating the cell migration. A.

<p>Self-assembled cell microarray screen of genes capable of regulating the migration of Hela cells by use of esiRNA tyrosine kinase library. <b>B.</b> Validation of the esiRNA screen results by use of siRNAs and transwell assay.</p

The normalization of esiRNA products.

<p><b>A.</b> A range of initial amounts of DNA template were assayed (100, 10, 1, and 0.1 ng, each in 5 µL in volume). After the immobilization and transcription steps, the variation of transcription products was within 20%. The final esiRNA products had a variation of less than 10% when the initial amount of DNA templates was in the range of 0.1–100 ng. <b>B</b>. Eight esiRNA products were manufactured in parallel. The standard deviation among these eight products was approximately 3%.</p

The silencing specificity and efficiency of esiRNAs. A.

<p>Fifteen GFP esiRNAs generated in parallel potently inhibited the fluorescent signal in cells cotransfected with GFP-encoding vectors; in contrast, five PLAU esiRNAs had no effect on the fluorescent intensity compared to control experiments. <b>B. & C.</b> Quantitative analysis of the silencing efficiency of esiRNA products. The qRT-PCR results showed that esiRNAs manufactured on the magnetic beads can efficiently inhibit expression levels of the respective genes. A western blot assay showed that esiRNAs targeting TP53, TGFB1, PLAU, or TGFBR2 inhibited therespective protein expression levels by up to approximately 50%.</p

Point-of-Care Multiplexed Assays of Nucleic Acids Using Microcapillary-based Loop-Mediated Isothermal Amplification

This report demonstrates a straightforward, robust, multiplexed and point-of-care microcapillary-based loop-mediated isothermal amplification (cLAMP) for assaying nucleic acids. This assay integrates capillaries (glass or plastic) to introduce and house sample/reagents, segments of water droplets to prevent contamination, pocket warmers to provide heat, and a hand-held flashlight for a visual readout of the fluorescent signal. The cLAMP system allows the simultaneous detection of two RNA targets of human immunodeficiency virus (HIV) from multiple plasma samples, and achieves a high sensitivity of two copies of standard plasmid. As few nucleic acid detection methods can be wholly independent of external power supply and equipment, our cLAMP holds great promise for point-of-care applications in resource-poor settings

Point-of-Care Multiplexed Assays of Nucleic Acids Using Microcapillary-based Loop-Mediated Isothermal Amplification

This report demonstrates a straightforward, robust, multiplexed and point-of-care microcapillary-based loop-mediated isothermal amplification (cLAMP) for assaying nucleic acids. This assay integrates capillaries (glass or plastic) to introduce and house sample/reagents, segments of water droplets to prevent contamination, pocket warmers to provide heat, and a hand-held flashlight for a visual readout of the fluorescent signal. The cLAMP system allows the simultaneous detection of two RNA targets of human immunodeficiency virus (HIV) from multiple plasma samples, and achieves a high sensitivity of two copies of standard plasmid. As few nucleic acid detection methods can be wholly independent of external power supply and equipment, our cLAMP holds great promise for point-of-care applications in resource-poor settings

Binding Affinity of Optimized Antibodies to SARS-CoV-2 Variants Spike.

Immobilized WT-RBD, Beta-RBD or Delta-S1 association (t = 0 to 180 s) and dissociation (t > 180 s) with REGN10987 (A) and optimized antibodies d7 (B), d9 (C), A3 (D) measured by surface plasmon resonance (SPR). (TIF)</p