@article {352,
	title = {Intensification: A Resource for Amplifying Population-Genetic Signals with Protein Repeats.},
	journal = {J Mol Biol},
	volume = {429},
	year = {2017},
	month = {2017 02 03},
	pages = {435-445},
	abstract = {<p>Large-scale genome sequencing holds great promise for the interpretation of protein structures through the discovery of many, rare functional variants in the human population. However, because protein-coding regions are under high selective constraints, these variants occur at low frequencies, such that there is often insufficient statistics for downstream calculations. To address this problem, we develop the Intensification approach, which uses the modular structure of repeat protein domains to amplify signals of selection from population genetics and traditional interspecies conservation. In particular, we are able to aggregate variants at the codon level to identify important positions in repeat domains that show strong conservation signals. This allows us to compare conservation over different evolutionary timescales. It also enables us to visualize population-genetic measures on protein structures. We make available the Intensification results as an online resource (http://intensification.gersteinlab.org) and illustrate the approach through a case study on the tetratricopeptide repeat.</p>},
	keywords = {Amino Acid Sequence, Chromosome Mapping, Codon, Computational Biology, Databases, Genetic, Evolution, Molecular, Genetics, Population, Humans, Internet, Molecular Structure, Protein Conformation, Proteins, Signal Processing, Computer-Assisted, X-Rays},
	issn = {1089-8638},
	doi = {10.1016/j.jmb.2016.12.003},
	author = {Chen, Jieming and Wang, Bo and Regan, Lynne and Gerstein, Mark}
}
@article {104,
	title = {Reads meet rotamers: structural biology in the age of deep sequencing.},
	journal = {Curr Opin Struct Biol},
	volume = {35},
	year = {2015},
	month = {2015 Dec},
	pages = {125-34},
	abstract = {<p>Structure has traditionally been interrelated with sequence, usually in the framework of comparing sequences across species sharing a common fold. However, the nature of information within the sequence and structure databases is evolving, changing the type of comparisons possible. In particular, we now have a vast amount of personal genome sequences from human populations and a greater fraction of new structures contain interacting proteins within large complexes. Consequently, we have to recast our conception of sequence conservation and its relation to structure-for example, focusing more on selection within the human population. Moreover, within structural biology there is less emphasis on the discovery of novel folds and more on relating structures to networks of protein interactions. We cover this changing mindset here. </p>},
	keywords = {High-Throughput Nucleotide Sequencing, Humans, Isomerism, Mutation, Proteins},
	issn = {1879-033X},
	doi = {10.1016/j.sbi.2015.11.003},
	author = {Sethi, Anurag and Clarke, Declan and Chen, Jieming and Kumar, Sushant and Galeev, Timur R and Regan, Lynne and Gerstein, Mark}
}
