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A common assumption in comparative genomics is that orthologous genes share greater functional similarity than do paralogous genes (the "ortholog conjecture"). Many methods used to computationally predict protein function are based on this assumption, even though it is largely untested. Here we present the first large-scale test of the ortholog conjecture(More)
An international consortium released the first draft sequence of the human genome 10 years ago. Although the analysis of this data has suggested the genetic underpinnings of many diseases, we have not yet been able to fully quantify the relationship between genotype and phenotype. Thus, a major current effort of the scientific community focuses on(More)
Large-scale tumor sequencing projects are now underway to identify genetic mutations that drive tumor initiation and development. Most studies take a gene-based approach to identifying driver mutations, highlighting genes mutated in a large percentage of tumor samples as those likely to contain driver mutations. However, this gene-based approach usually(More)
BACKGROUND AND OBJECTIVE With recent breakthroughs in high-throughput sequencing, identifying deleterious mutations is one of the key challenges for personalized medicine. At the gene and protein level, it has proven difficult to determine the impact of previously unknown variants. A statistical method has been developed to assess the significance of(More)
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