Proteomics counterattack, deep annotation genome

Is there a lack of innovation in applying for a project? No idea writing a paper? Is rushing to graduate time tight? Don't be afraid, for Jikai, everything is a routine! What's more, for the ultimate problem of the universe: "How does the silk rebel against Bai Fumei?" The old driver Huang Bo also has a classic case to share with everyone.

Once upon a time, in the field of biological research, there was a Baifumei called Genomics. She had a strong skill: DNA sequencing. With this skill, she completed genome sequencing of multiple species, localized coding genes and Identify basic genomic annotation tasks such as the structure of the coding gene. But her approach to genome annotation relies heavily on DNA and RNA sequence information. In order to more accurately interpret the genome to be sequenced, it is not enough to rely solely on her own efforts. It is also necessary to integrate multiple types of omics methods for genome annotation.

Bai Fumei wants to chase everyone, but this year, there is no innovation, how can you get beautiful? Come on, dry the bowl of steaming chicken soup!

The famous silk is shining! Dubbed Proteomics (Proteomics), the goddess has a crush on for years, suffering itself is not a skill, though long in the face of the goddess of wild brush sense of presence, but did not attract attention goddess. Therefore, for the genomics skills defects, devote themselves to cultivation, and finally won the unique skills - tandem mass spectrometry technology, to make up for the goddess imperfections, and finally counterattack success. This skill enables high coverage of the proteome, making it possible to perform genome annotation using tandem mass spectrometry data. The tandem mass spectrometry data can be used to verify the expression of the annotated gene on the one hand, and to correct the original annotated gene on the other hand, thereby discovering the new gene and re-annotating the genome sequence. In this way, it is a good way to make up for the deficiencies of genomics, so that it wins the favor of the goddess and wins the beauty. Become a biology research Smiths, they took to their combination did not name a very innovative - protein Genomics (Proteogenomics), meaning finger cross proteomics and genomics, the wide range and can cross A variety of ways to define, but usually refers to proteomics information research based on tandem mass spectrometry to improve annotation of the genome.

In June of this year, internationally renowned journals Nature and Cell reported the heroic deeds of the couple's ruthless attacks on breast cancer and ovarian cancer in the field of biological research using their powerful skills.

Which in Nature entitled "Proteogenomics connects somatic mutations to signalling in breast cancer" is described on the reports from   "Cancer Genome Atlas" (TCGA) , based on iTRAQ combined tandem mass spectrometry of 105 breast cancer samples representing four major breast cancer intrinsic types defined by mRNA, quantified more than 12,000 proteins and 33,000 phosphorylation sites Point proteomics and phosphorylation proteomics analysis .

For some breast cancer subtypes and tumors carrying common mutations such as PIK3CA and TP53 mutations, the results reveal some new protein markers and signaling pathways. In addition, copy number changes in some genes were linked to protein levels to identify 10 new candidate regulatory factors. Two of the candidate genes, SKP1 and CETN3, may be associated with the oncogene EGFR. EGFR is a particularly invasive breast cancer subtype, a marker of "basal cell-like" tumors. In addition, the phosphorylation status of some kinases was analyzed by isolated spots, highlighting some abnormally activated kinases in breast cancer samples such as HER2, CDK12, PAK1, PTK2, RIPK2 and TLK2. The result of the analysis is a high-quality proteomics resource for human breast cancer research, obtained using techniques and analytical methods that illustrate the link between the genome and the proteome. These data narrow the range of candidate driver genes in large deletion regions and amplification regions, identifying potential therapeutic targets.

In the report of Cell entitled "Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer" , 9600 proteins in the 169 tumor samples were identified using protein measurement and identification techniques based on iTRAQ combined tandem mass spectrometry , and The 3586 proteins commonly found in these samples were chosen for study . The tumor proteome of 169 ovarian cancer patients was analyzed to identify the key proteins present in their tumors. Ovarian cancer by proteomic aspects of those found with the known genomic data of these tumors together, so we re-recognize the most malignant ovarian serous ovarian cancer --- (serous ovarian cancer).

Although many people know that our genes play a role in cancer production, genes are often just a starting point. The gene is transcribed into RNA, which is then translated into protein. There are significant differences in the activity of these proteins, many of which affect their function and their interaction with other proteins. Cancer (especially high-grade serous ovarian cancer) is characterized by errors in genetic instructions. One scenario is that there are more copies of certain regions of the genome. These so-called copy number changes can lead to changes in protein abundance. In this new study, when comparing known genomic regions where copy number changes occur, the researchers found that parts of chromosomes 2, 7, 20, and 22 resulted in abundance of more than 200 proteins. A change has occurred.

Humans have not fully understood how complex cancer genomes can be transformed into driving biology that leads to relapse and death. Combining proteomics with genomics allows us to gain new insights into cancer while providing a valuable resource. So that the scientific community can use it to come up with new assumptions about these diseases and the means to treat them. Protein genomics will one day be proven to be a powerful clinical tool that enables humans to bridge the huge knowledge gap between cancer genomics and clinical effects.

In both cases, proteomics used a key trick in his unique stunt tandem mass spectrometry technology - iTRAQ (this trick is extremely lethal, as described above, no need to rumor here), using iTRAQ here Obtaining powerful proteomic data completes a deeper comment on the genome. The story of couples about protein genomics is introduced first, but their story is far from over. I believe that under their close cooperation, there will be new sparks, such as sequencing in genomics or The chip data is combined with the proteomics data obtained by iTRAQ for cross-group association analysis (the specific analysis method is not difficult, and can be discussed in detail by Huang Bo), thereby obtaining a panoramic view of the expression spectrum, and achieving complementarity and integration therebetween. Analyze the expression levels of genes and proteins in specific states of the organism; and obtain a broad understanding of differential expression profiles globally, and mine key proteins / genes regulated by post-transcription to find out some important biological regulation In addition, for some species whose protein database is not perfect, the protein sequence database is constructed by transcriptome data to improve the number of proteins identified in proteomics experiments.

I’ll talk about it today, next time we’ll talk about it?

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I won't tell you!

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