Expression analysis (RNA seq analysis) of children and adult data: Why is the Treehouse model novel?
Treehouse is harnessing the power of Big Data to benefit individual patients locally and globally. The researchers at Treehouse are using expression analysis (RNA sequence analysis) of children to establish methods to identify new treatment options for individual cancer patients. Treehouse mostly looks at mRNA expression, since these are the molecules that code for proteins and are typically measured in an RNA-Seq experiment.
To comprehend how this all happens at Treehouse, let’s first review DNA, RNA, transcription, translation and gene expression and their functions.
Many computational methods have been developed for analyzing differential gene expression. Big Data is being used to help children whose tumors do not have “adult” DNA mutations. They use big-data pan-cancer information to derive relative measurements of gene expression. Work is based on molecular classification of pediatric tumors based on gene expression analysis. This research aids in the identification of targeted therapies based on the increased expression of drug-targetable genes in the patient.
A little about DNA
DNA is the master blueprint for every cell in the human body. DNA carries the information for making all the cell’s proteins. These proteins implement all the functions of a living organism and determine the organism’s characteristics. https://science.howstuffworks.com/life/cellular-microscopic/dna5.htm
An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell. DNA contains the instructions for making proteins. When the cell reproduces, it must pass all this information on to the daughter cells. https://ghr.nlm.nih.gov/primer/basics/dna
So, what is RNA?
One of two types of nucleic acid made by cells, RNA (also called ribonucleic acid) contains information that has been copied from DNA (the other type of nucleic acid). Cells do not “understand” the message DNA conveys, so they need RNA to be the intermediary in the production of proteins. If DNA is a protein “blueprint,” then think of the RNA as the “carpenter” who reads the blueprint and carries out the building of the protein. Cells make several different forms of RNA, and each form has a specific job in the cell. https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=46568
There are four types of RNA that have different functions in the cell and have an important role in cell and protein synthesis:
- Messenger RNA (or mRNA) has the main role in transcription, or the first step in making a protein from a DNA blueprint.
- Transfer RNA (or tRNA) has the important job of making sure the correct amino acids are put into the polypeptide chain in the correct order during the translation process.
- Ribosomal RNA (or rRNA) is named for the organelle it makes up. An organelle is a specialized subunit within a cell that has a specific function. The ribosome is the eukaryotic cell organelle that helps assemble proteins. Since rRNA is the main building block of ribosomes, it has a very large and important role in translation.
- Also involved in gene expression is micro RNA (or miRNA). miRNA is a non-coding region of mRNA that is believed to be important in the either promotion or inhibition of gene expression. (4 Types of RNA by Heather Scoville)
An explanation of transcription and translation.
The process of building a protein is called transcription. Building proteins is very much like building a house:
- The master blueprint is DNA, which contains all the information to build the new protein (house).
- The working copy of the master blueprint is called messenger RNA (mRNA), which is copied from DNA.
- The construction site is either the cytoplasm in a prokaryote or the endoplasmic reticulum (ER) in a eukaryote.
- The building materials are amino acids.
- The construction workers are ribosomes and transfer RNA molecules.
https://science.howstuffworks.com/life/cellular-microscopic/dna5.htm
In a eukaryote, DNA never leaves the nucleus, so its information must be copied. This copying process is called transcription and the copy is mRNA. At any one moment, many genes are being transcribed simultaneously according to the cell’s needs for specific proteins. The working copy of the blueprint (mRNA) must now go to the construction site where the workers will build the new protein.
Translation is the assembly process. To continue with the house example, once the working copy of the blueprint has reached the site, the workers must assemble the materials according to the instructions; this process is called translation. In the case of a protein, the workers are the ribosomes and special RNA molecules called transfer RNA (tRNA). The construction materials are the amino acids.
- Translation occurs after the messenger RNA (mRNA) has carried the transcribed “message” from the DNA to protein-making factories in the cell, called ribosomes.
- The message carried by the mRNA is read by a carrier molecule called transfer RNA (tRNA).
- When the mRNA sequence is read, each tRNA molecule delivers its amino acid to the ribosome and binds temporarily to the corresponding codon on the mRNA molecule.
- Once the tRNA is bound, it releases its amino acid and the adjacent amino acids all join together into a long chain called a polypeptide.
- This process continues until a protein is formed. Proteins carry out most of the active functions of a cell.
Finally, what is gene expression?:
When the information stored in our DNA is converted into instructions for making proteins or other molecules, it is called gene expression. Gene expression is a tightly regulated process that allows a cell to respond to its changing environment. This is also a process by which a gene gets turned on in a cell to make RNA and proteins. Gene expression may be measured by looking at the RNA, or the protein made from the RNA, or what the protein does in a cell. As mentioned earlier, there are two key steps involved in making a protein — transcription and translation. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=537335
https://www.yourgenome.org/facts/what-is-gene-expression
How It Works
When genes are expressed, the genetic information (base sequence) on DNA is first transcribed (copied) to a molecule of messenger RNA (mRNA). The mRNA molecules then leave the cell nucleus and enter the cytoplasm, where they participate in protein synthesis by specifying the amino acids that make up individual proteins. https://www.ncbi.nlm.nih.gov/genome/probe/doc/ApplExpression.shtml
Finally
It is the dream of Treehouse that, every child with cancer has their genome and transcriptome sequenced and analyzed early in their disease and have access to all available treatments informed by genomics. Treehouse has gathered a compendium of RNA gene expression data which is made available for download and visualization for free. The data was processed with the RNA-Seq pipeline developed by the UC Santa Cruz Genomics Institute’s Computational Genomics Laboratory (CGL). The pipeline is available for general use; the source code is hosted on GitHub at BD2KGenomics/toil-rnaseq and a Dockerized version is available at UCSC-Treehouse/pipelines.
Recent Comments