Continuing down nostalgia lane, here is another old paper of mine:
Coelho, Luis Pedro, Tao Peng, and Robert F. Murphy. “Quantifying the Distribution of Probes Between Subcellular Locations Using Unsupervised Pattern Unmixing.” Bioinformatics 26.12 (2010): i7–i12. DOI: 10.1093/bioinformatics/btq220
I have already discussed the subcellular location determination problem. This is Given images of a protein, can we assign it to an organelle?
This is, however, a simplified version of the world: many proteins are present in multiple organelles. They may move between organelles in response to a stimulus or as part of the cell cycle. For example, here is an image of mitochondria in green (nuclei in red):
Here is one of lysosomes:
And here is a mix of both!:
This is a dataset constructed for the purpose of this work, so we know what is happening, but it simulates the situation where a protein is present in two locations simultaneously.
Thus, we can move beyond simple assignment of a protein to an organelle to assigning it to multiple organelles. In fact, some work (both from the Murphy group and others) has looked at subcellular location classification using multiple labels per image. This, however, is still not enough: we want to quantify this.
This is the pattern unmixing problem. The goal is to go from an image (or a set of images) to something like the following: This is 30% nuclear and 70% cytoplasmic, which is very different from 70% nuclear and 30% cytoplasmic. The basic organelles can serve as the base patterns .
Before our paper, there was some work in approaching this problem from a supervised perspective: Given examples of different organelles (ie, of markers that locate to a single organelle), can we automatically build a system which when given images of a protein which is distributed in multiple organelles, can figure out which fraction comes from each organelle?
Our paper extended this to work to the unsupervised case: can you learn a mixture when you do not know which are the basic patterns?
Determining the distribution of probes between different subcellular locations through automated unmixing of subcellular patterns Tao Peng, Ghislain M. C. Bonamy, Estelle Glory-Afshar, Daniel R. Rines, Sumit K. Chanda, and Robert F. Murphy PNAS 2010 107 (7) 2944-2949; published ahead of print February 1, 2010, doi:10.1073/pnas.0912090107
Object type recognition for automated analysis of protein subcellular location T Zhao, M Velliste, MV Boland, RF Murphy Image Processing, IEEE Transactions on 14 (9), 1351-1359
||This is still a limited model because we are not sure even how many base patterns we should consider, but it will do for now.