@article {49801, title = {Heterogeneity of transcription factor binding specificity models within and across cell lines}, journal = {Genome Research}, year = {2016}, month = {Apr-06-2017}, pages = {gr.199166.115}, issn = {1088-9051}, doi = {10.1101/gr.199166.115}, url = {http://genome.cshlp.org/lookup/doi/10.1101/gr.199166.115}, author = {Sharmin, Mahfuza and Bravo, {\'e}ctor Corrada and Hannenhalli, Sridhar} } @article {49723, title = {Harnessing the landscape of microbial culture media to predict new organism-media pairings.}, journal = {Nat Commun}, volume = {6}, year = {2015}, month = {2015}, pages = {8493}, abstract = {

Culturing microorganisms is a critical step in understanding and utilizing microbial life. Here we map the landscape of existing culture media by extracting natural-language media recipes into a Known Media Database (KOMODO), which includes >18,000 strain-media combinations, >3300 media variants and compound concentrations (the entire collection of the Leibniz Institute DSMZ repository). Using KOMODO, we show that although media are usually tuned for individual strains using biologically common salts, trace metals and vitamins/cofactors are the most differentiating components between defined media of strains within a genus. We leverage KOMODO to predict new organism-media pairings using a transitivity property (74\% growth in new in vitro experiments) and a phylogeny-based collaborative filtering tool (83\% growth in new in vitro experiments and stronger growth on predicted well-scored versus poorly scored media). These resources are integrated into a web-based platform that predicts media given an organism{\textquoteright}s 16S rDNA sequence, facilitating future cultivation efforts.

}, issn = {2041-1723}, doi = {10.1038/ncomms9493}, author = {Oberhardt, Matthew A and Zarecki, Raphy and Gronow, Sabine and Lang, Elke and Klenk, Hans-Peter and Gophna, Uri and Ruppin, Eytan} } @article {49797, title = {Heterogeneity of Transcription Factor binding specificity models within and across cell lines}, year = {2015}, doi = {10.1101/028787}, url = {http://biorxiv.org/lookup/doi/10.1101/028787}, author = {Sharmin, Mahfuza and Corrada Bravo, Hector and Hannenhalli, Sridhar S.} } @article {49624, title = {High throughput identification of cis-regulatory rewiring events in yeast.}, journal = {Mol Biol Evol}, year = {2015}, month = {2015 Sep 23}, abstract = {

A co-regulated module of genes ("regulon") can have evolutionarily conserved expression patterns and yet have diverged upstream regulators across species. For instance, the ribosomal genes regulon is regulated by the transcription factor (TF) TBF1 in C. albicans, while in S. cerevisiae it is regulated by RAP1. Only a handful of such rewiring events have been established, and the prevalence or conditions conducive to such events are not well known. Here, we develop a novel probabilistic scoring method to comprehensively screen for regulatory rewiring within regulons across 23 yeast species. Investigation of 1713 regulons and 176 TFs yielded 5353 significant rewiring events at 5\% FDR. Besides successfully recapitulating known rewiring events, our analyses also suggests TF candidates for certain processes reported to be under distinct regulatory controls in S. cerevisiae and C. albicans, for which the implied regulators are not known: 1) oxidative stress response (Sc-MSN2 to Ca-FKH2),and 2) nutrient modulation (Sc-RTG1 to Ca-GCN4/Ca-UME6). Further, a stringent screen to detect TF rewiring at individual genes identified 1446 events at 10\% FDR. Overall, these events are supported by strong co-expression between the predicted regulator and its target gene(s) in a species-specific fashion (>50-fold). Independent functional analyses of rewiring TF pairs revealed greater functional interactions and shared biological processes between them (p=1e-03).Our study represents the first comprehensive assessment of regulatory rewiring; with a novel approach that has generated a unique high-confidence resource of several specific events, suggesting that evolutionary rewiring is relatively frequent and may be a significant mechanism of regulatory innovation.

}, issn = {1537-1719}, doi = {10.1093/molbev/msv203}, author = {Sarda, Shrutii and Hannenhalli, Sridhar} } @article {49861, title = {The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes}, journal = {Genome biology}, volume = {15}, year = {2014}, pages = {524}, author = {Todd Treangen and Ondov, Brian D and Koren, Sergey and Phillippy, Adam M} } @article {38327, title = {Hawkeye and AMOS: visualizing and assessing the quality of genome assemblies}, journal = {Briefings in bioinformaticsBriefings in bioinformatics}, volume = {14}, year = {2013}, publisher = {Oxford University Press}, author = {Schatz, Michael C. and Phillippy, Adam M. and Sommer, Daniel D. and Delcher, Arthur L. and Puiu, Daniela and Narzisi, Giuseppe and Salzberg, Steven L. and M. Pop} } @article {49727, title = {Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase.}, journal = {Nature}, volume = {477}, year = {2011}, month = {2011 Sep 8}, pages = {225-8}, abstract = {

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.

}, keywords = {Animals, Bilirubin, Cell Line, Cells, Cultured, Citric Acid Cycle, Computer simulation, Fumarate Hydratase, Fumarates, Genes, Lethal, Genes, Tumor Suppressor, Glutamine, Heme, Heme Oxygenase (Decyclizing), Kidney Neoplasms, Leiomyomatosis, Mice, Mitochondria, Mutation, NAD, Neoplastic Syndromes, Hereditary, Skin Neoplasms, Uterine Neoplasms}, issn = {1476-4687}, doi = {10.1038/nature10363}, author = {Frezza, Christian and Zheng, Liang and Folger, Ori and Rajagopalan, Kartik N and MacKenzie, Elaine D and Jerby, Livnat and Micaroni, Massimo and Chaneton, Barbara and Adam, Julie and Hedley, Ann and Kalna, Gabriela and Tomlinson, Ian P M and Pollard, Patrick J and Watson, Dave G and Deberardinis, Ralph J and Shlomi, Tomer and Ruppin, Eytan and Gottlieb, Eyal} } @article {49850, title = {Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes}, journal = {PLoS Genet}, volume = {7}, year = {2011}, pages = {e1001284}, author = {Todd Treangen and Eduardo Rocha} } @article {38331, title = {Hopx and Hdac2 Interact to Modulate Gata4 Acetylation and Embryonic Cardiac Myocyte Proliferation}, journal = {Developmental CellDevelopmental Cell}, volume = {19}, year = {2010}, type = {10.1016/j.devcel.2010.08.012}, abstract = {SummaryRegulation of chromatin structure via histone modification has recently received intense attention. Here,~we demonstrate that the chromatin-modifying enzyme histone deacetylase 2 (Hdac2) functions with a small homeodomain factor, Hopx, to mediate deacetylation of Gata4, which is expressed by cardiac progenitor cells and plays critical roles in the regulation of cardiogenesis. In the absence of Hopx and Hdac2 in mouse embryos, Gata4 hyperacetylation is associated with a marked increase in~cardiac myocyte proliferation, upregulation of Gata4 target genes, and perinatal lethality. Hdac2 physically interacts with Gata4, and this interaction is stabilized by Hopx. The ability of Gata4 to transactivate cell cycle genes is impaired by Hopx/Hdac2-mediated deacetylation, and this effect is abrogated by loss of Hdac2-Gata4 interaction. These results suggest that Gata4 is a nonhistone target of Hdac2-mediated deacetylation and that Hdac2, Hopx, and Gata4 coordinately regulate cardiac myocyte proliferation during embryonic development.}, isbn = {1534-5807}, author = {Trivedi, Chinmay M. and Zhu, Wenting and Wang, Qiaohong and Jia, Cheng and Kee, Hae Jin and Li, Li and Sridhar Hannenhalli and Epstein, Jonathan A.} } @article {38328, title = {Hawkeye: an interactive visual analytics tool for genome assemblies}, journal = {Genome BiologyGenome Biology}, volume = {8}, year = {2007}, type = {10.1186/gb-2007-8-3-r34}, abstract = {Genome sequencing remains an inexact science, and genome sequences can contain significant errors if they are not carefully examined. Hawkeye is our new visual analytics tool for genome assemblies, designed to aid in identifying and correcting assembly errors. Users can analyze all levels of an assembly along with summary statistics and assembly metrics, and are guided by a ranking component towards likely mis-assemblies. Hawkeye is freely available and released as part of the open source AMOS project http://amos.sourceforge.net/hawkeye.}, isbn = {1465-6906}, author = {Schatz, Michael C. and Phillippy, Adam M. and Shneiderman, Ben and Salzberg, Steven L.} } @article {38330, title = {High-throughput sequence alignment using Graphics Processing Units}, journal = {BMC BioinformaticsBMC Bioinformatics}, volume = {8}, year = {2007}, type = {10.1186/1471-2105-8-474}, isbn = {1471-2105}, author = {Schatz, Michael C. and Trapnell, Cole and Delcher, Arthur L. and Varshney, Amitabh} } @article {49751, title = {How A.I. and multi-robot systems research will accelerate our understanding of social animal behavior}, volume = {94}, year = {2006}, pages = {1445-1463}, author = {Tucker Balch and Frank Dellaert and Adam Feldman and Andrew Guillory and Charles Isbell and Zia Khan and Andrew Stein and Hank Wilde} } @article {49561, title = {How Multirobot Systems Research will Accelerate our Understanding of Social Animal Behavior}, volume = {94}, year = {2006}, month = {Jan-07-2006}, pages = {1445 - 1463}, issn = {0018-9219}, doi = {10.1109/JPROC.2006.876969}, url = {http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1677955}, author = {Balch, T. and Dellaert, F. and Feldman, A. and Guillory, A. and Isbell, C.L. and Khan, Z. and Pratt, S.C. and Stein, A.N. and Wilde, H.} } @article {38329, title = {Hierarchical Scaffolding With Bambus}, journal = {Genome ResearchGenome Research}, volume = {14}, year = {2004}, type = {10.1101/gr.1536204}, abstract = {The output of a genome assembler generally comprises a collection of contiguous DNA sequences (contigs) whose relative placement along the genome is not defined. A procedure called scaffolding is commonly used to order and orient these contigs using paired read information. This ordering of contigs is an essential step when finishing and analyzing the data from a whole-genome shotgun project. Most recent assemblers include a scaffolding module; however, users have little control over the scaffolding algorithm or the information produced. We thus developed a general-purpose scaffolder, called Bambus, which affords users significant flexibility in controlling the scaffolding parameters. Bambus was used recently to scaffold the low-coverage draft dog genome data. Most significantly, Bambus enables the use of linking data other than that inferred from mate-pair information. For example, the sequence of a completed genome can be used to guide the scaffolding of a related organism. We present several applications of Bambus: support for finishing, comparative genomics, analysis of the haplotype structure of genomes, and scaffolding of a mammalian genome at low coverage. Bambus is available as an open-source package from our Web site.}, author = {M. Pop and Kosack, Daniel S. and Salzberg, Steven L.} } @article {38326, title = {Hardness of flip-cut problems from optical mapping}, journal = {Journal of Computational BiologyJournal of Computational Biology}, volume = {4}, year = {1997}, author = {Dan{\v C}{\'I}K, V. and Sridhar Hannenhalli and Muthukrishnan, S.} }