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Another Proteomics Point of View

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In the past you have covered Craig Venter’s every word on proteomics without presenting other views and possibilities. Why not review other ideas?

For example, one of the central problems is the business model which is a collection of computers and instruments all obtained from catalogues, maintained under contract, and with all reagents and support supplied from the outside. Since the technology is widely known, it is easy (especially now) to hire staff. No one in the business of genomics actually develops the instruments required except Applera, and that is not done at Celera. Actually the working insides of the machines used at Celera are of Japanese manufacture.

Nobel prizes for sequencing were given in 1980 and the project has been an obvious one since then. (Actually we wrote the original proposals for both the genome and proteome projects in 1980 and 1983.) So-called “big science” always builds its own machines, and the design and development of these is an integral part of the project.

Proteomics will not be big science until it integrates all of the parts under one project. The parts are precision cell fractionation, 2DE, MS in all its forms, development of libraries of full-length clones (see our web page), development of libraries of high-affinity antibodies, and the development of a human protein index to tell us where individual genes are actually expressed.

2D gels are a pain, are central to all of proteomics, and everyone would like a dry-fingered substitute. Hence, the urgent stress on mass spectrometry, which is not a substitute for 2DE. We are the only company that has bit the bullet and automated 2DE. But that is not the real story.

The real story is that drugs and disease rarely produce a qualitative change (i.e., the appearance or total disappearance) of a protein gene product. Hence what is wanted in the end is a quantitative global analysis of cells and tissues. That requires quantitative 2DE on a massive scale to the pharmaceutical work now required.

To get the dynamic range, precision quantitative cell fractionation is required — something not even talked about except here. Mass spec is absolutely essential to proteomics and has revolutionized it. However 2DE has no present substitute, and it remains a difficult system to work with without automation, which we have.

One of the central problems in proteomics is that it does not have a prediction-generating theoretical foundation. That requires discussion.

Norman G. Anderson, PhD, Chief Scientist, Large Scale Biology Corporation

 

Begging Major-Player Status

In Aaron Sender’s article “Better Genomics Through Chemistry,” (March 2002, p. 40), you name a variety of companies, but Xencor was not listed and is a major player in the field of chemical genetics.

Using its ProCode technology, Xencor can quickly analyze libraries of expressed proteins from humans, animals, plants, and microbes for protein-small molecule and protein-protein interactions, critical in assessing protein function. This proprietary technology uniquely combines protein expression in a wide range of native cell types, including human cells, with the ease of DNA detection to deliver a billion-fold improvement in speed and sensitivity over standard proteomics tools such as mass spectrometry.

ProCode is enabling the field of chemical genomics by connecting drug molecules to the genes they act upon. In fact, the company has generated a database of genes that interact with existing drugs, potential drugs, and certain chemicals to accelerate the discovery of new therapeutics and agricultural products.

Navjot Rai, Account Executive, Mentus

 

The Scan

Expanded Genetic Testing Uncovers Hereditary Cancer Risk in Significant Subset of Cancer Patients

In Genome Medicine, researchers found pathogenic or likely pathogenic hereditary cancer risk variants in close to 17 percent of the 17,523 patients profiled with expanded germline genetic testing.

Mitochondrial Replacement Therapy Embryos Appear Largely Normal in Single-Cell 'Omics Analyses

Embryos produced with spindle transfer-based mitochondrial replacement had delayed demethylation, but typical aneuploidy and transcriptome features in a PLOS Biology study.

Cancer Patients Report Quality of Life Benefits for Immune Checkpoint Inhibitors

Immune checkpoint inhibitor immunotherapy was linked in JAMA Network Open to enhanced quality of life compared to other treatment types in cancer patients.

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.