Editing Functional genomics (section)

===At the RNA level===

====Microarrays====
{{Main|DNA microarray}}
[[File:DNA microarray.svg|thumb|A [[DNA microarray]]]]
Microarrays measure the amount of mRNA in a sample that corresponds to a given gene or probe DNA sequence. Probe sequences are immobilized on a solid surface and allowed to [[Nucleic acid hybridization|hybridize]] with fluorescently labeled "target" mRNA. The intensity of fluorescence of a spot is proportional to the amount of target sequence that has hybridized to that spot and therefore to the abundance of that mRNA sequence in the sample. Microarrays allow for the identification of candidate genes involved in a given process based on variation between transcript levels for different conditions and shared expression patterns with genes of known function.

====SAGE====
{{Main|Serial analysis of gene expression}}
[[Serial analysis of gene expression]] (SAGE) is an alternate method of analysis based on RNA sequencing rather than hybridization. SAGE relies on the sequencing of 10–17 base pair tags which are unique to each gene. These tags are produced from [[Polyadenylation|poly-A mRNA]] and ligated end-to-end before sequencing. SAGE gives an unbiased measurement of the number of transcripts per cell, since it does not depend on prior knowledge of what transcripts to study (as microarrays do).

====RNA sequencing====
{{Main|RNA-Seq|MicroRNA sequencing}}
RNA sequencing has taken over microarray and SAGE technology in recent years, as noted in 2016, and has become the most efficient way to study  transcription and gene expression. This is typically done by [[DNA sequencing|next-generation sequencing]].<ref>{{cite journal | vauthors = Hrdlickova R, Toloue M, Tian B | title = RNA-Seq methods for transcriptome analysis | journal = Wiley Interdisciplinary Reviews: RNA | volume = 8 | issue = 1 | pages = e1364 | date = January 2017 | pmid = 27198714 | pmc = 5717752 | doi = 10.1002/wrna.1364 }}</ref>

A subset of sequenced RNAs are small RNAs, a class of non-coding RNA molecules that are key regulators of transcriptional and post-transcriptional gene silencing, or [[RNA silencing]]. Next-generation sequencing is the gold standard tool for [[non-coding RNA]] discovery, profiling and expression analysis.

====Massively Parallel Reporter Assays (MPRAs)====
Massively parallel reporter assays is a technology to test the cis-regulatory activity of DNA sequences.<ref>{{cite journal | vauthors = Kwasnieski JC, Fiore C, Chaudhari HG, Cohen BA | title = High-throughput functional testing of ENCODE segmentation predictions | journal = Genome Research | volume = 24 | issue = 10 | pages = 1595–602 | date = October 2014 | pmid = 25035418 | pmc = 4199366 | doi = 10.1101/gr.173518.114 }}</ref><ref>{{cite journal | vauthors = Patwardhan RP, Hiatt JB, Witten DM, Kim MJ, Smith RP, May D, Lee C, Andrie JM, Lee SI, Cooper GM, Ahituv N, Pennacchio LA, Shendure J | title = Massively parallel functional dissection of mammalian enhancers in vivo | journal = Nature Biotechnology | volume = 30 | issue = 3 | pages = 265–70 | date = February 2012 | pmid = 22371081 | pmc = 3402344 | doi = 10.1038/nbt.2136 }}</ref> MPRAs use a [[plasmid]] with a synthetic cis-regulatory element upstream of a promoter driving a synthetic gene such as Green Fluorescent Protein. A library of cis-regulatory elements is usually tested using MPRAs, a library can contain from hundreds to thousands of cis-regulatory elements. The cis-regulatory activity of the elements is assayed by using the downstream reporter activity. The activity of all the library members is assayed in parallel using barcodes for each cis-regulatory element. One limitation of MPRAs is that the activity is assayed on a plasmid and may not capture all aspects of gene regulation observed in the genome.

====STARR-seq====
{{Main|STARR-seq}}
STARR-seq is a technique similar to MPRAs to assay enhancer activity of randomly sheared genomic fragments. In the original publication,<ref>{{cite journal | vauthors = Arnold CD, Gerlach D, Stelzer C, Boryń ŁM, Rath M, Stark A | title = Genome-wide quantitative enhancer activity maps identified by STARR-seq | journal = Science | volume = 339 | issue = 6123 | pages = 1074–7 | date = March 2013 | pmid = 23328393 | doi = 10.1126/science.1232542 | bibcode = 2013Sci...339.1074A | s2cid = 54488955 }}</ref> randomly sheared fragments of the ''Drosophila'' genome were placed downstream of a minimal promoter. Candidate enhancers amongst the randomly sheared fragments will transcribe themselves using the minimal promoter. By using sequencing as a readout and controlling for input amounts of each sequence the strength of putative enhancers are assayed by this method.

====Perturb-seq====
{{Main|Perturb-seq}}
[[File:Overview of Perturb-seq workflow.jpeg|thumb|517x517px|Overview of Perturb-seq workflow]]

Perturb-seq couples CRISPR mediated gene knockdowns with single-cell gene expression. Linear models are used to calculate the effect of the knockdown of a single gene on the expression of multiple genes.