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To compare entire genomes from different species, biologists increasingly need alignment methods that are efficient enough to handle long sequences, and accurate enough to correctly align the conserved biological features between distant species. We present LAGAN, a system for rapid global alignment of two homologous genomic sequences, and Multi-LAGAN, a(More)
We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about(More)
Computational efforts to identify functional elements within genomes leverage comparative sequence information by looking for regions that exhibit evidence of selective constraint. One way of detecting constrained elements is to follow a bottom-up approach by computing constraint scores for individual positions of a multiple alignment and then defining(More)
Many DNA variants have been identified on more than 300 diseases and traits using Genome-Wide Association Studies (GWASs). Some have been validated using deep sequencing, but many fewer have been validated functionally, primarily focused on non-synonymous coding SNPs (nsSNPs). It is an open question whether synonymous coding SNPs (sSNPs) and other(More)
This paper addresses the problem of aligning multiple sequences of non-coding RNA genes. We approach this problem with the biologically motivated paradigm that scoring of ncRNA alignments should be based primarily on secondary structure rather than nucleotide conservation. We introduce a novel graph theoretic model (NLG) for analyzing algorithms based on(More)
Predicting ad click-through rates (CTR) is a massive-scale learning problem that is central to the multi-billion dollar online advertising industry. We present a selection of case studies and topics drawn from recent experiments in the setting of a deployed CTR prediction system. These include improvements in the context of traditional supervised learning(More)
Here, we demonstrate how comparative sequence analysis facilitates genome-wide base-pair-level interpretation of individual genetic variation and address two questions of importance for human personal genomics: first, whether an individual's functional variation comes mostly from noncoding or coding polymorphisms; and, second, whether population-specific or(More)
  • D Sculley, Gary Holt, Daniel Golovin, Eugene Davydov, Todd Phillips, Dietmar Ebner +2 others
  • 2014
Machine learning offers a fantastically powerful toolkit for building complex systems quickly. This paper argues that it is dangerous to think of these quick wins as coming for free. Using the framework of technical debt, we note that it is remarkably easy to incur massive ongoing maintenance costs at the system level when applying machine learning. The(More)
Machine learning offers a fantastically powerful toolkit for building useful complex prediction systems quickly. This paper argues it is dangerous to think of these quick wins as coming for free. Using the software engineering framework of technical debt, we find it is common to incur massive ongoing maintenance costs in real-world ML systems. We explore(More)
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