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1.  Pathprinting: An integrative approach to understand the functional basis of disease 
Genome Medicine  2013;5(7):68.
New strategies to combat complex human disease require systems approaches to biology that integrate experiments from cell lines, primary tissues and model organisms. We have developed Pathprint, a functional approach that compares gene expression profiles in a set of pathways, networks and transcriptionally regulated targets. It can be applied universally to gene expression profiles across species. Integration of large-scale profiling methods and curation of the public repository overcomes platform, species and batch effects to yield a standard measure of functional distance between experiments. We show that pathprints combine mouse and human blood developmental lineage, and can be used to identify new prognostic indicators in acute myeloid leukemia. The code and resources are available at http://compbio.sph.harvard.edu/hidelab/pathprint
doi:10.1186/gm472
PMCID: PMC3971351  PMID: 23890051
2.  The Stem Cell Discovery Engine: an integrated repository and analysis system for cancer stem cell comparisons 
Nucleic Acids Research  2011;40(Database issue):D984-D991.
Mounting evidence suggests that malignant tumors are initiated and maintained by a subpopulation of cancerous cells with biological properties similar to those of normal stem cells. However, descriptions of stem-like gene and pathway signatures in cancers are inconsistent across experimental systems. Driven by a need to improve our understanding of molecular processes that are common and unique across cancer stem cells (CSCs), we have developed the Stem Cell Discovery Engine (SCDE)—an online database of curated CSC experiments coupled to the Galaxy analytical framework. The SCDE allows users to consistently describe, share and compare CSC data at the gene and pathway level. Our initial focus has been on carefully curating tissue and cancer stem cell-related experiments from blood, intestine and brain to create a high quality resource containing 53 public studies and 1098 assays. The experimental information is captured and stored in the multi-omics Investigation/Study/Assay (ISA-Tab) format and can be queried in the data repository. A linked Galaxy framework provides a comprehensive, flexible environment populated with novel tools for gene list comparisons against molecular signatures in GeneSigDB and MSigDB, curated experiments in the SCDE and pathways in WikiPathways. The SCDE is available at http://discovery.hsci.harvard.edu.
doi:10.1093/nar/gkr1051
PMCID: PMC3245064  PMID: 22121217
3.  Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin 
A free-energy-based approach is used to describe the mechanism through which chaperonin-containing TCP-1 (CCT) folds the filament-forming cytoskeletal protein actin, which is one of its primary substrates. The experimental observations on the actin folding and unfolding pathways are collated and then re-examined from this perspective, allowing us to determine the position of the CCT intervention on the actin free-energy folding landscape. The essential role for CCT in actin folding is to provide a free-energy contribution from its ATP cycle, which drives actin to fold from a stable, trapped intermediate I3, to a less stable but now productive folding intermediate I2. We develop two hypothetical mechanisms for actin folding founded upon concepts established for the bacterial type I chaperonin GroEL and extend them to the much more complex CCT system of eukaryotes. A new model is presented in which CCT facilitates free-energy transfer through direct coupling of the nucleotide hydrolysis cycle to the phases of actin substrate maturation.
doi:10.1098/rsif.2008.0185
PMCID: PMC2570749  PMID: 18708324
actin; chaperonin-containing TCP-1; protein folding; chaperones; free-energy landscapes

Results 1-3 (3)