Comparing and Contrasting ChIP-seq and ChIP-chip

There are many different flavors of chromatin immunoprecipitation (ChIP) experiments. Depending one what kinds of protein-DNA interactions you want to see , you may apply different methods. Traditionally, the general workflow of ChIP requires sequencing of the purified DNA fragments that come out of solution with the protein of interest. This method is also known as ChIP-seq. Another methodology combines the ChIP technique with a microarray output. Purified DNA fragments are subjected to an array of nucleotide strands. This presents a different methodology for reading out results.

Advantages and Disadvantages of Each Method
The introduction of the microarray in ChIP-chip allows for a dramatically faster acquisition of data. It is also significantly cheaper to buy a chip arrayed with different nucleotide sequences. However, a number of disadvantages are also present in ChIP-chip experiments. First, the ability to identify any element in the chromatin is limited to the types of nucleotide sequences that have been coupled to the chip. So if your DNA sequence bound to protein is absent on the ChIP, you will see a false negative result. Typically, with millions of oligonucleotides coupled to a single chip, your coverage will be good enough to get a result, but there is the chance that you will see a false result.

Another significant disadvantage of ChIP-chip is resolution. Since you are using oligonucleotides that are thirty to one hundred base pairs long, this is the size of a fragment you can reasonably identify. If your purified DNA binds to only ten out of one hundred, you will not be able to tell which ten were bound using ChIP-chip. ChIP-seq circumvents this problem by requiring de novo sequencing of the bound DNA. This allows the resolution to be as high as one nucleotide. Therefore, ChIP-seq data tends to be much more clear.

ChIP-seq also presents some technical advantages over ChIP-chip. Specifically, the amount of purified DNA needed and the amplification required are different. ChIP-chip requires both high amount of DNA and long amplification steps to generate a high enough signal. ChIP-seq can start from a very small amount of DNA. Since sequencing is so sensitive, the results can be read with very little amplification.

One other area where ChIP-seq gains a cost effectiveness advantage is in multiplexing. This refers to the ability to perform multiple experiments at once. ChIP-chip cannot perform multiplexing because the results will be impossible to interpret. This is because once the DNA has hybridized with the oligonucleotides, it is not possible to differentiate different strands. By using different amplification primers, one can easily isolate and read the sequences of multiple purified DNA fragments using ChIP-seq.