Even the most die-hard genomics aficionados can admit that proteomics is having a moment: researchers are asking more protein-based questions to uncover new biology.
For example, Anne Carpenter, PhD, senior director of the Imaging Platform and institute scientist at the Broad Institute, told GEN that her whole career is predicated on asking the question, “Can we pivot from ‘all genomics all of the time’?” Because, she said, action in the cell is happening at the proteomics level. In turn, with this enthusiasm, new technologies to enable more proteomics abound.
Perhaps the developers of novel proteomics technologies could see this moment coming. For example, the technology that underlies Nomic Bio’s proteomics assay was developed over a decade ago, when Milad Dagher, PhD, co-founder and CEO of Nomic Bio, was a PhD student. Dagher had a background in electrical engineering and was excited to work in nanotechnology; he was working on the first radio amplifier in carbon nanotubes when his plans changed. He met David Juncker, PhD, professor in the Department of Biomedical Engineering at McGill University, who impressed upon Dagher the importance of measuring proteins and the challenges that existed in the space. And Juncker, specifically, focused on solving the problem of cross-reactivity in multiplexed immunoassays.
After developing the nELISA assay together, with other lab members, the Montreal-based Nomic Bio spun out of Juncker’s lab in 2019 to provide a proteomics service—a model the company still adopts. The nELISA assay has, as Dagher explained, “a lot of familiar components to it”: an antibody-based sandwich immunoassay and a flow cytometry readout (not FACS). So, it may seem familiar. But Dagher quickly asserts that it is “fundamentally different.”
One distinction is that every antibody pair is pre-assembled onto its own bead. Mixing antibodies, Dagher noted, leads to “a world of trouble.” To stay out of trouble, the capture and detection antibodies are immobilized together. The idea, the company stated, is to reduce cross-reactivity. Another distinction is flow cytometry, not sequencing. Dagher said that it is more cost-efficient and flexible, but recognizes that it sounds “sort of weird,” especially for those in the sequencing space.
Before the assay is started, the antibody sandwich is loaded on a color-coded bead. The detection antibody is tethered using a flexible DNA linker. The sample is added and will bind if the protein is recognized. To be detected, the assay uses a method of displacement. A fluorescently labeled DNA oligo is added, which displaces and labels the detection antibody. If there is no target, the antibodies are displaced and washed away.
There are two colors used in the system: the displacing oligo has a detection dye, which is used for the readout. That is used to determine the presence (and the concentration) of the protein on the bead. In addition, each bead is color-coded using a set of dyes.
To do the barcoding, Nomic mixes four dyes in different intensity levels to create a four-dye code that can be decoded and read out on the cytometer. The four dyes mix at different levels in every bead, which gives the code for that bead and allows for 3,000 barcodes that can be read out on a regular flow cytometer. The four-color dyes are decoded first to determine the identity of that protein, and then the protein can be quantified.
Since the company launched in 2018, it has offered the ability to detect hundreds of proteins. Specifically, an inflammatory panel with roughly 280 proteins. But now, the company is launching new offerings. First, a (non-customizable) 1,000 plex panel—the OMNIplex 1000. Dagher noted that the cost for this service is as little as $50 per sample, and the turnaround time is as little as one week.
Other new offerings include a cardiometabolic panel of 288 proteins (taken from the 1,000) and a custom panel of up to 288 proteins, also taken from the 1,000.
Swagatam Mukhopadhyay, PhD, CIO & co-founder at Creyon Bio, used the technology to support their N-of-1 drug in which they dosed a TNPO2 patient. He told GEN that “the team at Nomic Bio was able to provide the raw data in a format I could easily work with, allowing me to do my own analysis, a very nice supplement to what they did.” An additional feature of their assay, he noted, is the small volume of material needed to actually run the assay. “Since the amount of clinical CSF available for the study was extremely limited, knowing we didn’t need much to conduct our analysis was great,” he added.
Carpenter also worked with Nomic on two large-scale projects (both of which were in-kind donations by Nomic). One is the Omics for Assessing Signatures for Integrated Safety (OASIS) Consortium, which is working to develop non-animal systems. Their mission, Carpenter told GEN, is to try to figure out whether cell painting (the technology Carpenter developed), transcriptomics, and proteomics can be used to predict liver toxicity. The group tests every compound—roughly 1,500—known to cause liver toxicity in various cellular systems, including organoids. They asked, “Do any combinations of the models and readouts lead to liver toxicity prediction that is better than animals?” The group has just started on the proteomic work, and has done just one pilot plate with Nomic.
Carpenter worked with Nomic previously on another large-scale project: the JUMP-Cell Painting Consortium. The goal of that project was to create a big, image-based data set of genetics and drug perturbations. Carpenter was excited because she “never thought we would be able to include proteomics at a decent scale.”
Nomic is entering an increasingly crowded market. But Dagher thinks the time is right. Where proteomics is today, he added, is nowhere near where NGS and genomics are from a perspective of market adoption. But one thing to remember is that the majority of scientists are outside looking in on proteomics, he said. They can’t afford proteomics or think it’s too complex.
But there has never been a moment, he said, when there has been a stronger realization of the importance of proteomics. “I think everyone realizes how important it is to add proteomics into our biological information data stack.”
The post Proteomic Technology From Nomic Flows to 1,000 Plex appeared first on GEN - Genetic Engineering and Biotechnology News.
For example, Anne Carpenter, PhD, senior director of the Imaging Platform and institute scientist at the Broad Institute, told GEN that her whole career is predicated on asking the question, “Can we pivot from ‘all genomics all of the time’?” Because, she said, action in the cell is happening at the proteomics level. In turn, with this enthusiasm, new technologies to enable more proteomics abound.
Perhaps the developers of novel proteomics technologies could see this moment coming. For example, the technology that underlies Nomic Bio’s proteomics assay was developed over a decade ago, when Milad Dagher, PhD, co-founder and CEO of Nomic Bio, was a PhD student. Dagher had a background in electrical engineering and was excited to work in nanotechnology; he was working on the first radio amplifier in carbon nanotubes when his plans changed. He met David Juncker, PhD, professor in the Department of Biomedical Engineering at McGill University, who impressed upon Dagher the importance of measuring proteins and the challenges that existed in the space. And Juncker, specifically, focused on solving the problem of cross-reactivity in multiplexed immunoassays.
After developing the nELISA assay together, with other lab members, the Montreal-based Nomic Bio spun out of Juncker’s lab in 2019 to provide a proteomics service—a model the company still adopts. The nELISA assay has, as Dagher explained, “a lot of familiar components to it”: an antibody-based sandwich immunoassay and a flow cytometry readout (not FACS). So, it may seem familiar. But Dagher quickly asserts that it is “fundamentally different.”
One distinction is that every antibody pair is pre-assembled onto its own bead. Mixing antibodies, Dagher noted, leads to “a world of trouble.” To stay out of trouble, the capture and detection antibodies are immobilized together. The idea, the company stated, is to reduce cross-reactivity. Another distinction is flow cytometry, not sequencing. Dagher said that it is more cost-efficient and flexible, but recognizes that it sounds “sort of weird,” especially for those in the sequencing space.
Before the assay is started, the antibody sandwich is loaded on a color-coded bead. The detection antibody is tethered using a flexible DNA linker. The sample is added and will bind if the protein is recognized. To be detected, the assay uses a method of displacement. A fluorescently labeled DNA oligo is added, which displaces and labels the detection antibody. If there is no target, the antibodies are displaced and washed away.
There are two colors used in the system: the displacing oligo has a detection dye, which is used for the readout. That is used to determine the presence (and the concentration) of the protein on the bead. In addition, each bead is color-coded using a set of dyes.
To do the barcoding, Nomic mixes four dyes in different intensity levels to create a four-dye code that can be decoded and read out on the cytometer. The four dyes mix at different levels in every bead, which gives the code for that bead and allows for 3,000 barcodes that can be read out on a regular flow cytometer. The four-color dyes are decoded first to determine the identity of that protein, and then the protein can be quantified.
Since the company launched in 2018, it has offered the ability to detect hundreds of proteins. Specifically, an inflammatory panel with roughly 280 proteins. But now, the company is launching new offerings. First, a (non-customizable) 1,000 plex panel—the OMNIplex 1000. Dagher noted that the cost for this service is as little as $50 per sample, and the turnaround time is as little as one week.
Other new offerings include a cardiometabolic panel of 288 proteins (taken from the 1,000) and a custom panel of up to 288 proteins, also taken from the 1,000.
Swagatam Mukhopadhyay, PhD, CIO & co-founder at Creyon Bio, used the technology to support their N-of-1 drug in which they dosed a TNPO2 patient. He told GEN that “the team at Nomic Bio was able to provide the raw data in a format I could easily work with, allowing me to do my own analysis, a very nice supplement to what they did.” An additional feature of their assay, he noted, is the small volume of material needed to actually run the assay. “Since the amount of clinical CSF available for the study was extremely limited, knowing we didn’t need much to conduct our analysis was great,” he added.
Carpenter also worked with Nomic on two large-scale projects (both of which were in-kind donations by Nomic). One is the Omics for Assessing Signatures for Integrated Safety (OASIS) Consortium, which is working to develop non-animal systems. Their mission, Carpenter told GEN, is to try to figure out whether cell painting (the technology Carpenter developed), transcriptomics, and proteomics can be used to predict liver toxicity. The group tests every compound—roughly 1,500—known to cause liver toxicity in various cellular systems, including organoids. They asked, “Do any combinations of the models and readouts lead to liver toxicity prediction that is better than animals?” The group has just started on the proteomic work, and has done just one pilot plate with Nomic.
Carpenter worked with Nomic previously on another large-scale project: the JUMP-Cell Painting Consortium. The goal of that project was to create a big, image-based data set of genetics and drug perturbations. Carpenter was excited because she “never thought we would be able to include proteomics at a decent scale.”
Nomic is entering an increasingly crowded market. But Dagher thinks the time is right. Where proteomics is today, he added, is nowhere near where NGS and genomics are from a perspective of market adoption. But one thing to remember is that the majority of scientists are outside looking in on proteomics, he said. They can’t afford proteomics or think it’s too complex.
But there has never been a moment, he said, when there has been a stronger realization of the importance of proteomics. “I think everyone realizes how important it is to add proteomics into our biological information data stack.”
The post Proteomic Technology From Nomic Flows to 1,000 Plex appeared first on GEN - Genetic Engineering and Biotechnology News.