title: Inter-species pathway perturbation prediction via data-driven detection of functional homology.
abstract: BACKGROUND
  Experiments in animal models are often conducted to infer how humans will respond to stimuli by assuming that the same biological pathways will be affected in both organisms. The limitations of this assumption were tested in the IMPROVER Species Translation Challenge, where 52 stimuli were applied to both human and rat cells and perturbed pathways were identified. In the Inter-species Pathway Perturbation Prediction sub-challenge, multiple teams proposed methods to use rat transcription data from 26 stimuli to predict human gene set and pathway activity under the same perturbations. Submissions were evaluated using three performance metrics on data from the remaining 26 stimuli.
  
  
  RESULTS
  We present two approaches, ranked second in this challenge, that do not rely on sequence-based orthology between rat and human genes to translate pathway perturbation state but instead identify transcriptional response orthologs across a set of training conditions. The translation from rat to human accomplished by these so-called direct methods is not dependent on the particular analysis method used to identify perturbed gene sets. In contrast, machine learning-based methods require performing a pathway analysis initially and then mapping the pathway activity between organisms. Unlike most machine learning approaches, direct methods can be used to predict the activation of a human pathway for a new (test) stimuli, even when that pathway was never activated by a training stimuli.
  
  
  BACKGROUND
  Gene expression data are available from ArrayExpress (accession E-MTAB-2091), while software implementations are available from http://bioinformaticsprb.med.wayne.edu?p=50 and http://goo.gl/hJny3h.
  
  
  BACKGROUND
  christoph.hafemeister@nyu.edu or atarca@med.wayne.edu.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hafemeister
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Erhan
authors.initials: E
authors.lastname: Bilal
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Norel
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Kahn
authors.initials: K
authors.lastname: Rhrissorrakrai
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.affiliation: Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA Department of Biology, Center for Genomics & Systems Biology, New York University, New York, NY 10003, Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD and Detroit, MI 48201, USA, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, Computer Science Department, Courant institute of Mathematical Sciences, New York University, New York, NY 10012 and Department of Computer Science, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
mesh_terms: D000465:Algorithms; D000818:Animals; D001185:Artificial Intelligence; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D016208:Databases, Factual; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D012984:Software; D013045:Species Specificity; D049490:Systems Biology / Q000379:methods*; D057170:Translational Research, Biomedical
chemical_list: D016207:Cytokines; D010750:Phosphoproteins