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PubMed Central Canada to be taken offline in February 2018

On February 23, 2018, PubMed Central Canada (PMC Canada) will be taken offline permanently. No author manuscripts will be deleted, and the approximately 2,900 manuscripts authored by Canadian Institutes of Health Research (CIHR)-funded researchers currently in the archive will be copied to the National Research Council’s (NRC) Digital Repository over the coming months. These manuscripts along with all other content will also remain publicly searchable on PubMed Central (US) and Europe PubMed Central, meaning such manuscripts will continue to be compliant with the Tri-Agency Open Access Policy on Publications.

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1.  Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016 
Alsayegh, Mohammad A. | Alshamali, Hanan | Khadada, Mousa | Ciccolini, Amanda | Ellis, Anne K. | Quint, Diana | Powley, William | Lee, Laurie | Fiteih, Yahya | Baksh, Shairaz | Vliagoftis, Harissios | Gerega, Sebastien K. | Millson, Brad | Charland, Katia | Barakat, Stephane | Sun, Xichun | Jimenez, Ricardo | Waserman, Susan | FitzGerald, Mark J. | Hébert, Jacques | Cognet-Sicé, Josiane | Renahan, Kevin E. | Huq, Saiful | Chooniedass, Rishma | Sawyer, Scott | Pasterkamp, Hans | Becker, Allan | Smith, Steven G. | Zhang, Shiyuan | Jayasundara, Kavisha | Tacon, Claire | Simidchiev, Alex | Nadeau, Gilbert | Gunsoy, Necdet | Mullerova, Hana | Albers, Frank | Kim, Young Woong | Shannon, Casey P. | Singh, Amrit | Neighbour, Helen | Larché, Mark | Tebbutt, Scott J. | Klopp, Annika | Vehling, Lorena | Becker, Allan B. | Subbarao, Padmaja | Mandhane, Piushkumar J. | Turvey, Stuart E. | Sears, Malcolm R. | Azad, Meghan B. | Loewen, Keely | Monchka, Barret | Mahmud, Salaheddin M. | Jong, Geert ‘t | Longo, Cristina | Bartlett, Gillian | Ducharme, Francine M. | Schuster, Tibor | MacGibbon, Brenda | Barnett, Tracie | North, Michelle L. | Brook, Jeff | Lee, Elizabeth | Omana, Vanessa | Thiele, Jenny | Steacy, Lisa M. | Evans, Greg | Diamond, Miriam | Sussman, Gordon L. | Amistani, Yann | Abiteboul, Kathy | Tenn, Mark W. | Yang, ChenXi | Carlsten, Christopher | Conway, Edward M. | Mack, Douglas | Othman, Yasmin | Barber, Colin M. | Kalicinsky, Chrystyna | Burke, Andrea E. | Messieh, Mary | Nair, Parameswaran | Che, Chun T. | Douglas, Lindsay | Liem, Joel | Duan, Lucy | Miller, Charlotte | Dupuis, Pascale | Connors, Lori A. | Fein, Michael N. | Shuster, Joseph | Hadi, Hani | Polk, Brooke | Raje, Nikita | Labrosse, Roxane | Bégin, Philippe | Paradis, Louis | Roches, Anne Des | Lacombe-Barrios, Jonathan | Mishra, Sanju | Lacuesta, Gina | Chiasson, Meredith | Haroon, Babar | Robertson, Kara | Issekutz, Thomas | Leddin, Desmond | Couban, Stephen | Connors, Lori | Roos, Adrienne | Kanani, Amin | Chan, Edmond S. | Schellenberg, Robert | Rosenfield, Lana | Cvetkovic, Anna | Woodward, Kevin | Quirt, Jaclyn | Watson, Wade T. A. | Castilho, Edson | Sullivan, Jennifer A. | Temple, Beverley | Martin, Donna | Cook, Victoria E. | Mills, Christopher | Portales-Casamar, Elodie | Fu, Lisa W. | Ho, Alexander | Zaltzman, Jeffrey | Chen, Lucy | Vadas, Peter | Gabrielli, Sofianne | Clarke, Ann | Eisman, Harley | Morris, Judy | Joseph, Lawrence | LaVieille, Sebastien | Ben-Shoshan, Moshe | Graham, François | Barnes, Charles | Portnoy, Jay | Stagg, Vincent | Simons, Elinor | Lefebvre, Diana | Dai, David | Mandhane, Piushkumar | Sears, Malcolm | Tam, Herman | Simons, F. Estelle R. | Alotaibi, Dhaifallah | Dawod, Bassel | Tunis, Matthew C. | Marshall, Jean | Desjardins, Marylin | Béland, Marianne | Lejtenyi, Duncan | Drolet, Jean-Phillipe | Lemire, Martine | Tsoukas, Christos | Noya, Francisco J.D. | Alizadehfar, Reza | McCusker, Christine T. | Mazer, Bruce D. | Maestre-Batlle, Danay | Gunawan, Evelyn | Rider, Christopher F. | Bølling, Anette K. | Pena, Olga M. | Suez, Daniel | Melamed, Isaac | Hussain, Iftikhar | Stein, Mark | Gupta, Sudhir | Paris, Kenneth | Fritsch, Sandor | Bourgeois, Christelle | Leibl, Heinz | McCoy, Barbara | Noel, Martin | Yel, Leman | Scott, Ori | Reid, Brenda | Atkinson, Adelle | Kim, Vy Hong-Diep | Roifman, Chaim M. | Grunebaum, Eyal | AlSelahi, Eiman | Aleman, Fernando | Oberle, Amber | Trus, Mike | Sussman, Gordon | Kanani, Amin S. | Chambenoi, Olivier | Chiva-Razavi, Sima | Grodecki, Savannah | Joshi, Nikhil | Menikefs, Peter | Holt, David | Pun, Teresa | Tworek, Damian | Hanna, Raphael | Heroux, Delia | Rosenberg, Elli | Stiemsma, Leah | Turvey, Stuart | Denburg, Judah | Mill, Christopher | Teoh, Timothy | Zimmer, Preeti | Avinashi, Vishal | Paina, Mihaela | Darwish Hassan, Ahmed A. | Oliveria, John Paul | Olesovsky, Chris | Gauvreau, Gail | Pedder, Linda | Keith, Paul K. | Plunkett, Greg | Bolner, Michelle | Pourshahnazari, Persia | Stark, Donald | Vostretsova, Kateryna | Moses, Andrew | Wakeman, Andrew | Singer, Alexander | Gerstner, Thomas | Abrams, Elissa | Johnson, Sara F. | Woodgate, Roberta L.
doi:10.1186/s13223-017-0192-y
PMCID: PMC5390240
2.  Laboratory Animal Management Assistant (LAMA): a LIMS for active research colonies 
Laboratory Animal Management Assistant (LAMA) is an internet-based system for tracking large laboratory mouse colonies. It has a user-friendly interface with powerful search capabilities that ease day-to-day tasks such as tracking breeding cages and weaning litters. LAMA was originally developed to manage hundreds of new mouse strains generated by a large functional genomics program, the Pleiades Promoter Project (http://www.pleiades.org). The software system has proven to be highly flexible, suitable for diverse management approaches to mouse colonies. It allows custom tagging and grouping of animals, simplifying project-specific handling and access to data. Finally, LAMA was developed in close collaboration with mouse technicians to ease the transition from paper- or Excel-based management systems to computerized tracking, allowing data export in a popular spreadsheet format and automatic printing of cage cards. LAMA is an open-access software tool, freely available to the research community at http://launchpad.net/mousedb.
doi:10.1007/s00335-010-9258-6
PMCID: PMC5047758  PMID: 20411264 CAMSID: cams2250
3.  Proceedings of the Canadian society of allergy and clinical immunology annual scientific meeting 2015 
Côté, Marie-Ève | Boulay, Marie-Ève | Plante, Sophie | Chakir, Jamila | Boulet, Louis-Philippe | Ahmed, Hanan | Ospina, Maria-Beatriz | Sideri, Kyriaki | Vliagoftis, Harissios | Johnson, Sara F. | Woodgate, Roberta L. | Cros, Guilhem | Teira, Pierre | Cellot, Sonia | Bittencourt, Henrique | Decaluwe, Helene | Vachon, Marie France | Duval, Michel | Haddad, Elie | Kim, Vy H. D. | Pham-Huy, Anne | Grunebaum, Eyal | Oliveria, John-Paul | Phan, Stephanie | Tenn, Mark W. | Tworek, Damian | Smith, Steven G. | Baatjes, Adrian J. | Obminski, Caitlin D. | Munoz, Caroline E. | Scime, Tara X. | Sehmi, Roma | Gauvreau, Gail M. | Salter, Brittany M. | Smith, Steven G. | Obminski, Caitlin D. | Munoz, Caroline E. | Schlatman, Abbey | Scime, Tara X. | Watson, Rick | Sherkat, Roya | Khoshnevisan, Razieh | Sheikhbahaei, Saba | Betschel, Stephen | Warrington, Richard | Schellenberg, Robert | Fein, Michael N. | Pelletier, Jean-Philippe | Kan, Manstein | Labrosse, Roxane | Mak, Raymond | Loh, James | Kanani, Amin | Nowak, Dominik A. | Keith, Paul K. | Pannozzo, Daniel | Lima, Hermenio C. | Pham, Diana | Pham, Hoang | Alvarez, Gonzalo G. | Bencze, Istvan T. | Sharma, Krishna B. | Smith, Mark | Aaron, Shawn | Block, Jennifer | Keays, Tara | Leech, Judith | Schneidermen, David | Cameron, Jodi | Forgie, Jennifer | Ring, Alicia | O’Quinn, John W. | Santucci, Stephanie | Yang, William H. | Gaudet, Ena | Aaron, Shawn | Voisin, Mathew R. | Borici-Mazi, Rozita | Vostretsova, Kateryna | Stark, Donald F. | Yeboah, Elizabeth | Martin-Rhee, Michelle | Gula, Cheryl | Cheng, Clare | Paltser, Geoff | Dery, Alizée | Clarke, Ann | Nadeau, Kari | Harada, Laurie | Weatherall, Kimberley | Greenwood, Celia | Daley, Denise | Asai, Yuka | Ben-Shoshan, Moshe | Ling, Ling | Ospina, Maria B. | Protudjer, Jennifer L. P. | Vetander, Mirja | van Hage, Marianne | Olén, Ola | Wickman, Magnus | Bergström, Anna | Teoh, Timothy | Mill, Christopher | Wong, Tiffany | Baerg, Ingrid | Alexander, Angela | Hildebrand, Kyla J. | Dean, John | Kuzeljevic, Boris | Chan, Edmond S. | Argeny, Jonathan | Gona-Hoepler, Mia | Fucik, Petra | Nachbaur, Edith | Gruber, Saskia | Crameri, Reto | Glaser, Andreas | Szépfalusi, Zsolt | Rhyner, Claudio | Eiwegger, Thomas | Plunkett, Greg | Mire, Brad | Yazicioglu, Mehtap | Can, Ceren | Ciplak, Gokce | Cook, Victoria E. | Portales-Casamar, Elodie | Nashi, Emil P. | Gabrielli, Sofianne | Primeau, Marie-Noel | Lejtenyi, Christine | Netchiporouk, Elena | Dery, Alizee | Shand, Greg | Hoe, Erica | Liem, Joel | Ko, Jason K. | Huang, David J. T. | Mazza, Jorge A. | McHenry, Mary | Otley, Anthony | Watson, Wade | Kraft, John N. | Paina, Mihaela | Darwish Hassan, Ahmed A. | Heroux, Delia | Crawford, Lynn | Gauvreau, Gail | Denburg, Judah | Pedder, Linda | Chad, Zave | Sussman, Gordon | Hébert, Jacques | Frankish, Charles | Olynych, Timothy | Cheema, Amarjit | Del Carpio, Jaime | Harrison, Rachel | Torabi, Bahar | Medoff, Elaine | Mill, Jennifer | Quirt, Jaclyn A. | Wen, Xia | Kim, Jonathan | Herrero, Angel Jimenez | Kim, Harold L. | Grzyb, Magdalena J. | Primeau, Marie-Noël | Azad, Meghan B. | Lu, Zihang | Becker, Allan B. | Subbarao, Padmaja | Mandhane, Piushkumar J. | Turvey, Stuart E. | Sears, Malcolm R. | Boucher-Lafleur, Anne-Marie | Gagné-Ouellet, Valérie | Jacques, Éric | Laprise, Catherine | Chen, Michael | McGovern, Toby | Adner, Mikael | Martin, James G. | Cosic, Nela | Ntanda, Henry | Giesbrecht, Gerald | Kozyrskyj, Anita | Letourneau, Nicole | Dawod, Bassel | Marshall, Jean | De Schryver, Sarah | Halbrich, Michelle | La Vieille, Sebastian | Eisman, Harley | Alizadehfar, Reza | Joseph, Lawrence | Morris, Judy | Feldman, Laura Y. | Thacher, Jesse D. | Kull, Inger | Melén, Erik | Pershagen, Göran | Protudjer, Jennifer L. P. | Hosseini, Ali | Hackett, Tillie L. | Hirota, Jeremy | McNagny, Kelly | Wilson, Susan | Carlsten, Chris | Huq, Saiful | Chooniedass, Rishma | Gerwing, Brenda | Huang, Henry | Lefebvre, Diana | Becker, Allan | Khamis, Mona M. | Awad, Hanan | Allen, Kevin | Adamko, Darryl J. | El-Aneed, Anas | Kim, Young Woong | Gliddon, Daniel R. | Shannon, Casey P. | Singh, Amrit | Hickey, Pascal L. C. | Ellis, Anne K. | Neighbour, Helen | Larche, Mark | Tebbutt, Scott J. | Ladouceur, Erika | Stewart, Miriam | Evans, Josh | Masuda, Jeff | To, Teresa | King, Malcolm | Larouche, Miriam | Liang, Liming | Legere, Stephanie A. | Haidl, Ian D. | Legaré, Jean-Francois | Marshall, Jean S. | Sears, Malcolm | Moraes, Theo J. | Ratjen, Felix | Gustafsson, Per | Lou, Wendy | North, Michelle L. | Lee, Elizabeth | Omana, Vanessa | Thiele, Jenny | Brook, Jeff | Rahman, Tanvir | Lejtenyi, Duncan | Fiter, Ryan | Piccirillo, Ciriaco | Mazer, Bruce | Simons, Elinor | Hildebrand, Kyla | Turvey, Stuart | DeMarco, Mari | Le Cao, Kim-Anh | Gauvreau, Gail M. | Mark FitzGerald, J. | O’Byrne, Paul M. | Stiemsma, Leah T. | Arrieta, Marie-Claire | Cheng, Jasmine | Dimitriu, Pedro A. | Thorson, Lisa | Yurist, Sophie | Lefebvre, Diana L. | Mandhane, Piush | McNagny, Kelly M. | Kollmann, Tobias | Mohn, William W. | Brett Finlay, B. | Tran, Maxwell M. | Lefebvre, Diana L. | Ramasundarahettige, Chinthanie F. | Dai, Wei Hao | Mandhane, Piush J. | Tworek, Damian | O’Byrne, Seamus N. | O’Byrne, Paul M. | Denburg, Judah A. | Walsh, Laura | Soliman, Mena | Steacy, Lisa M. | Adams, Daniel E. | Warner, Linda | Mauro, Mary Ann | Mamonluk, Robby | Yang, ChenXi | Conway, Ed M.
Table of contents
A1 Role of fibrocytes in allergic rhinitis
Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet
A2 Patterns of aeroallergens sensitization in Northern Alberta
Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis
A3 Addressing acceptable risk for adolescents with Food-Induced Anaphylaxis (FIA)
Sara F. Johnson, Roberta L. Woodgate
A4 Outcomes of matched related and unrelated bone marrow transplantation after reduced-toxicity conditioning for children suffering from Chronic Granulomatous Disease
Guilhem Cros, Pierre Teira, Sonia Cellot, Henrique Bittencourt, Helene Decaluwe, Marie France Vachon, Michel Duval, Elie Haddad
A5 Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario
Vy H.D. Kim, Anne Pham-Huy, Eyal Grunebaum
A6 Detection of regulatory B cells in the airways of subjects with asthma
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Damian Tworek, Steven G. Smith, Adrian J. Baatjes, Caitlin D. Obminski, Caroline E. Munoz, Tara X. Scime, Roma Sehmi, Gail M Gauvreau
A7 Characterization of IgE-expressing B cells in the airways and peripheral blood of allergic asthmatic subjects
John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Brittany M Salter, Steven G Smith, Caitlin D Obminski, Caroline E Munoz, Abbey Schlatman, Tara X Scime, Rick Watson, Roma Sehmi, Gail M Gauvreau
A8 Pregnancy: could it be a risk factor for primary immunodeficient patients
Roya Sherkat, Razieh Khoshnevisan, Saba Sheikhbahaei
A9 Clinical experience with Octagam: a Canadian retrospective chart review
Stephen Betschel, Richard Warrington, Robert Schellenberg
A10 Kounis syndrome secondary to contrast media with inferior ST elevations and bilateral ischemic stroke
Michael N Fein, Jean-Philippe Pelletier
A11 Honey bee venom immunotherapy ineffective in bumble bee-induced anaphylaxis: case report and review of literature
Manstein Kan, Robert Schellenberg
A12 Delayed immune reconstitution occurring after multiple immune complications of hematological stem cell transplantation for a leaky SCID
Roxane Labrosse, Guilhem Cros, Pierre Teira, Henrique Bittencourt, Helene Decaluwe, Michel Duval, Elie Haddad
A13 Comparison of Three Case Reports of Acquired Angioedema: presentation, management and outcome
Raymond Mak, James Loh, Amin Kanani
A14 Sitagliptin-associated angioedema not related to concurrent use of ARB or ACE inhibitor
Dominik A. Nowak, Paul K. Keith
A15 Sneddon-Wilkinson subcorneal pustular dermatosis associated with an IgA monoclonal gammopathy
Daniel Pannozzo, Dominik A. Nowak, Hermenio C. Lima
A16 Omalizumab can be effective in patients with allergic bronchopulmonary aspergillosis
Diana Pham, Hoang Pham, Gonzalo G. Alvarez, Istvan T. Bencze, Krishna B. Sharma, Mark Smith, Shawn Aaron, Jennifer Block, Tara Keays, Judith Leech, David Schneidermen, Jodi Cameron, Jennifer Forgie, Alicia Ring, John W. O’Quinn, Stephanie Santucci, William H. Yang
A17 Efficacious use of omalizumab in the treatment of cystic fibrosis
Diana Pham, Hoang Pham, Ena Gaudet, Shawn Aaron, Stephanie Santucci, William H. Yang
A18 HAE with normal C1-INH with inconsistent response to C1 esterase inhibitor infusion but reliably responsive to icatibant
Hoang Pham, Stephanie Santucci, William H. Yang
A19 Anaphylaxis reaction to lactase enzyme
Mathew R. Voisin, Rozita Borici-Mazi
A20 Risk of solid tumor malignancies in patients with primary immune deficiency
Kateryna Vostretsova, Donald F. Stark
A21 Is it time to adopt the chromogenic assay for measuring C1 esterase inhibitor function in patients with HAE Type 2?
Elizabeth Yeboah, Paul K. Keith
A22 Emergency department visits for anaphylaxis and allergic reactions
Michelle Martin-Rhee, Cheryl Gula, Clare Cheng, Geoff Paltser
A23 START: Susceptibility To food Allergies in a Registry of Twins
Alizée Dery, Ann Clarke, Kari Nadeau, Laurie Harada, Kimberley Weatherall, Celia Greenwood, Denise Daley, Yuka Asai, Moshe Ben-Shoshan
A24 Qualifying the diagnostic approach employed by allergists when managing patients with self-diagnosed non-celiac gluten sensitivity (NCGS)
Lee Horgan, Teresa Pun
A25 Retrospective analysis on the agreement between skin prick test and serum food specific IgE antibody in adults with suspected food allergy
Ling Ling, Maria B. Ospina, Kyriaki Sideri, Harissios Vliagoftis
A26 Staple food hypersensitivity from infancy to adolescence: a report from the BAMSE cohort
Jennifer L.P. Protudjer, Mirja Vetander, Marianne van Hage, Ola Olén, Magnus Wickman, Anna Bergström
A27 Evaluating the impact of supervised epinephrine autoinjector administration during food challenges on perceived parent confidence
Timothy Teoh, Christopher Mill, Tiffany Wong, Ingrid Baerg, Angela Alexander, Kyla J. Hildebrand, John Dean, Boris Kuzeljevic, Edmond S. Chan
A28 Local immunoglobulin production to Aspergillus fumigatus cystic fibrosis
Jonathan Argeny, Mia Gona-Hoepler, Petra Fucik, Edith Nachbaur, Saskia Gruber, Reto Crameri, Andreas Glaser, Zsolt Szépfalusi, Claudio Rhyner, Thomas Eiwegger
A29 Extract consumption with skin prick test (SPT) devices
Greg. Plunkett, Brad Mire
A30 Evaluation of our cases with nonsteroidal anti-inflammatory drug reactions
Mehtap Yazicioglu, Ceren Can, Gokce Ciplak
A31 Reasons for referral and final diagnoses in a tertiary care pediatric allergy clinic
Victoria E. Cook, Kyla J. Hildebrand, Elodie Portales-Casamar, Christopher Mill, Edmond S. Chan
A32 Internist referral practices for inpatients with self-reported penicillin allergies at a tertiary care teaching hospital
Michael N Fein, Emil P Nashi
A33 Assessing the risk of reactions in children with a negative oral challenge after a subsequent use of amoxicillin
Sofianne Gabrielli, Christopher Mill, Marie-Noel Primeau, Christine Lejtenyi, Elena Netchiporouk, Alizee Dery, Greg Shand, Moshe Ben-Shoshan
A34 Validity of self-reported penicillin allergies
Erica Hoe, Joel Liem
A35 Effectiveness of allergy-test directed elimination diets in eosinophilic esophagitis
Jason K. Ko, David J.T. Huang, Jorge A. Mazza
A36 Allergy testing and dietary management in pediatric eosinophilic esophagitis (EoE): A retrospective review of a tertiary Canadian centre’s experience
Mary McHenry, Anthony Otley,Wade Watson
A37 Visualizing the impact of atopic and allergic skin disease
Dominik A. Nowak, John N. Kraft
A38 Cystic fibrosis with and without nasal polyposis in pediatric patients: a cross-sectional comparative study
Mihaela Paina, Ahmed A. Darwish Hassan, Delia Heroux, Lynn Crawford, Gail Gauvreau, Judah Denburg, Linda Pedder, Paul K. Keith
A39 Evaluation of macrolide antibiotic hypersensitivity: the role of oral challenges in children
Bahar Torabi, Marie-Noel Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A40 Venom allergy testing: is a graded approach necessary?
Jaclyn A. Quirt, Xia Wen, Jonathan Kim, Angel Jimenez Herrero, Harold L. Kim
A41 The role of oral challenges in evaluating cephalosporin hypersensitivity reactions in children
Magdalena J. Grzyb, Marie-Noël Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan
A42 Breastfeeding and infant wheeze, atopy and atopic dermatitis: findings from the Canadian Healthy Infant Longitudinal Development Study
Meghan B. Azad, Zihang Lu, Allan B. Becker, Padmaja Subbarao, Piushkumar J. Mandhane, Stuart E. Turvey, Malcolm R. Sears, the CHILD Study Investigators
A43 IL33 DNA methylation in bronchial epithelial cells is associated to asthma
Anne-Marie Boucher-Lafleur, Valérie Gagné-Ouellet, Éric Jacques, Sophie Plante, Jamila Chakir, Catherine Laprise
A44 NRF2 mediates the antioxidant response to organic dust-induced oxidative stress in bronchial epithelial cells
Michael Chen, Toby McGovern, Mikael Adner, James G. Martin
A45 The effects of perinatal distress, immune biomarkers and mother-infant interaction quality on childhood atopic dermatitis (rash) at 18 months
Nela Cosic, Henry Ntanda, Gerald Giesbrecht, Anita Kozyrskyj, Nicole Letourneau
A46 Examining the immunological mechanisms associated with cow’s milk allergy
Bassel Dawod, Jean Marshall
A47 Tryptase levels in children presenting with anaphylaxis to the Montréal Children’s Hospital
Sarah De Schryver, Michelle Halbrich, Ann Clarke, Sebastian La Vieille, Harley Eisman, Reza Alizadehfar, Lawrence Joseph, Judy Morris, Moshe Ben-Shoshan
A48 Secondhand tobacco smoke exposure in infancy and the development of food hypersensitivity from childhood to adolescence
Laura Y. Feldman, Jesse D. Thacher, Inger Kull, Erik Melén, Göran Pershagen, Magnus Wickman, Jennifer L. P. Protudjer, Anna Bergström
A49 Combined exposure to diesel exhaust and allergen enhances allergic inflammation in the bronchial submucosa of atopic subjects
Ali Hosseini, Tillie L. Hackett, Jeremy Hirota, Kelly McNagny, Susan Wilson, Chris Carlsten
A50 Comparison of skin-prick test measurements by an automated system against the manual method
Saiful Huq, Rishma Chooniedass, Brenda Gerwing, Henry Huang, Diana Lefebvre, Allan Becker
A51 The accurate identification and quantification of urinary biomarkers of asthma and COPD through the use of novel DIL- LC-MS/MS methods
Mona M. Khamis, Hanan Awad, Kevin Allen, Darryl J. Adamko, Anas El-Aneed
A52 Systemic immune pathways associated with the mechanism of Cat-Synthetic Peptide Immuno-Regulatory Epitopes, a novel immunotherapy, in whole blood of cat-allergic people
Young Woong Kim, Daniel R. Gliddon, Casey P. Shannon, Amrit Singh, Pascal L. C. Hickey, Anne K. Ellis, Helen Neighbour, Mark Larche, Scott J. Tebbutt
A53 Reducing the health disparities: online support for children with asthma and allergies from low-income families
Erika Ladouceur, Miriam Stewart, Josh Evans, Jeff Masuda, Nicole Letourneau, Teresa To, Malcolm King
A54 Epigenetic association of PSORS1C1 and asthma in the Saguenay-Lac-Saint-Jean asthma study
Miriam Larouche, Liming Liang, Catherine Laprise
A55 IL-33 induces cytokine and chemokine production in human mast cells
Stephanie A. Legere, Ian D. Haidl, Jean-Francois Legaré, Jean S. Marshall
A56 Reference ranges for lung clearance index from infancy to adolescence for Canadian population
Zihang Lu, Malcolm Sears, Theo J. Moraes, Felix Ratjen, Per Gustafsson, Wendy Lou, Padmaja Subbarao
A57 Kingston Allergy Birth Cohort: cohort profile and mother/child characteristics to age 2
Michelle L. North, Elizabeth Lee, Vanessa Omana, Jenny Thiele, Jeff Brook, Anne K. Ellis
A58 Cow’s milk protein specific IgE, IgA and IgG4 as a predictor of outcome in oral immunotherapy
Tanvir Rahman, Duncan Lejtenyi, Sarah De Schryver, Ryan Fiter, Ciriaco Piccirillo, Moshe Ben-Shoshan, Bruce Mazer
A59 Age of peanut introduction and development of reactions and sensitization to peanut
Elinor Simons, Allan B. Becker, Rishma Chooniedass, Kyla Hildebrand, Edmond S. Chan, Stuart Turvey, Padmaja Subbarao, Malcolm Sears
A60 Multi-omic blood biomarker signatures of the late phase asthmatic response
Amrit Singh, Casey P. Shannon, Young Woong Kim, Mari DeMarco, Kim-Anh Le Cao, Gail M. Gauvreau, J. Mark FitzGerald, Louis-Philippe Boulet, Paul M. O’Byrne, Scott J. Tebbutt
A61 Early life gut microbial alterations in children diagnosed with asthma by three years of age
Leah T. Stiemsma, Marie-Claire Arrieta, Jasmine Cheng, Pedro A. Dimitriu, Lisa Thorson, Sophie Yurist, Boris Kuzeljevic, Diana L. Lefebvre, Padmaja Subbarao, Piush Mandhane, Allan Becker, Malcolm R. Sears, Kelly M. McNagny, Tobias Kollmann, the CHILD Study Investigators, William W. Mohn, B. Brett Finlay, Stuart E. Turvey
A62 The relationship between food sensitization and atopic dermatitis at age 1 year in a Canadian birth cohort
Maxwell M. Tran, Diana L. Lefebvre, Chinthanie F. Ramasundarahettige, Allan B. Becker, Wei Hao Dai, Padmaja Subbarao, Piush J. Mandhane, Stuart E. Turvey, Malcolm R. Sears
A63 Allergen inhalation enhances Toll-like receptor-induced thymic stromal lymphopoietin receptor expression by hematopoietic progenitor cells in mild asthmatics
Damian Tworek, Delia Heroux, Seamus N. O’Byrne, Paul M. O’Byrne, Judah A. Denburg
A64 The Allergic Rhinitis Clinical Investigator Collaborative – replicated eosinophilia on repeated cumulative allergen challenges in nasal lavage samples
Laura Walsh, Mena Soliman, Jenny Thiele, Lisa M. Steacy, Daniel E. Adams, Anne K. Ellis
A65 The CHILD Study: optimizing subject retention in pediatric longitudinal cohort research
Linda Warner, Mary Ann Mauro, Robby Mamonluk, Stuart E. Turvey
A66 Differential expression of C3a and C5a in allergic asthma
ChenXi Yang, Amrit Singh, Casey P. Shannon, Young Woong Kim, Ed M. Conway, Scott J. Tebbutt
doi:10.1186/s13223-016-0118-0
PMCID: PMC5009563
4.  DNA methylation signature of human fetal alcohol spectrum disorder 
Background
Prenatal alcohol exposure is the leading preventable cause of behavioral and cognitive deficits, which may affect between 2 and 5 % of children in North America. While the underlying mechanisms of alcohol’s effects on development remain relatively unknown, emerging evidence implicates epigenetic mechanisms in mediating the range of symptoms observed in children with fetal alcohol spectrum disorder (FASD). Thus, we investigated the effects of prenatal alcohol exposure on genome-wide DNA methylation in the NeuroDevNet FASD cohort, the largest cohort of human FASD samples to date.
Methods
Genome-wide DNA methylation patterns of buccal epithelial cells (BECs) were analyzed using the Illumina HumanMethylation450 array in a Canadian cohort of 206 children (110 FASD and 96 controls). Genotyping was performed in parallel using the Infinium HumanOmni2.5-Quad v1.0 BeadChip.
Results
After correcting for the effects of genetic background, we found 658 significantly differentially methylated sites between FASD cases and controls, with 41 displaying differences in percent methylation change >5 %. Furthermore, 101 differentially methylated regions containing two or more CpGs were also identified, overlapping with 95 different genes. The majority of differentially methylated genes were highly expressed at the level of mRNA in brain samples from the Allen Brain Atlas, and independent DNA methylation data from cortical brain samples showed high correlations with BEC DNA methylation patterns. Finally, overrepresentation analysis of genes with up-methylated CpGs revealed a significant enrichment for neurodevelopmental processes and diseases, such as anxiety, epilepsy, and autism spectrum disorders.
Conclusions
These findings suggested that prenatal alcohol exposure is associated with distinct DNA methylation patterns in children and adolescents, raising the possibility of an epigenetic biomarker of FASD.
Electronic supplementary material
The online version of this article (doi:10.1186/s13072-016-0074-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s13072-016-0074-4
PMCID: PMC4926300  PMID: 27358653
5.  rAAV-compatible MiniPromoters for restricted expression in the brain and eye 
Molecular Brain  2016;9:52.
Background
Small promoters that recapitulate endogenous gene expression patterns are important for basic, preclinical, and now clinical research. Recently, there has been a promising revival of gene therapy for diseases with unmet therapeutic needs. To date, most gene therapies have used viral-based ubiquitous promoters–however, promoters that restrict expression to target cells will minimize off-target side effects, broaden the palette of deliverable therapeutics, and thereby improve safety and efficacy. Here, we take steps towards filling the need for such promoters by developing a high-throughput pipeline that goes from genome-based bioinformatic design to rapid testing in vivo.
Methods
For much of this work, therapeutically interesting Pleiades MiniPromoters (MiniPs; ~4 kb human DNA regulatory elements), previously tested in knock-in mice, were “cut down” to ~2.5 kb and tested in recombinant adeno-associated virus (rAAV), the virus of choice for gene therapy of the central nervous system. To evaluate our methods, we generated 29 experimental rAAV2/9 viruses carrying 19 different MiniPs, which were injected intravenously into neonatal mice to allow broad unbiased distribution, and characterized in neural tissues by X-gal immunohistochemistry for icre, or immunofluorescent detection of GFP.
Results
The data showed that 16 of the 19 (84 %) MiniPs recapitulated the expression pattern of their design source. This included expression of: Ple67 in brain raphe nuclei; Ple155 in Purkinje cells of the cerebellum, and retinal bipolar ON cells; Ple261 in endothelial cells of brain blood vessels; and Ple264 in retinal Müller glia.
Conclusions
Overall, the methodology and MiniPs presented here represent important advances for basic and preclinical research, and may enable a paradigm shift in gene therapy.
Electronic supplementary material
The online version of this article (doi:10.1186/s13041-016-0232-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s13041-016-0232-4
PMCID: PMC4862195  PMID: 27164903
rAAV Gene therapy; Raphe nuclei; Purkinje cells; Retina; Cornea
6.  Profiling placental and fetal DNA methylation in human neural tube defects 
Background
The incidence of neural tube defects (NTDs) declined by about 40 % in Canada with the introduction of a national folic acid (FA) fortification program. Despite the fact that few Canadians currently exhibit folate deficiency, NTDs are still the second most common congenital abnormality. FA fortification may have aided in reducing the incidence of NTDs by overcoming abnormal one carbon metabolism cycling, the process which provides one carbon units for methylation of DNA. We considered that NTDs persisting in a folate-replete population may also occur in the context of FA-independent compromised one carbon metabolism, and that this might manifest as abnormal DNA methylation (DNAm). Second trimester human placental chorionic villi, kidney, spinal cord, brain, and muscle were collected from 19 control, 22 spina bifida, and 15 anencephalic fetuses in British Columbia, Canada. DNA was extracted, assessed for methylenetetrahydrofolate reductase (MTHFR) genotype and for genome-wide DNAm using repetitive elements, in addition to the Illumina Infinium HumanMethylation450 (450k) array.
Results
No difference in repetitive element DNAm was noted between NTD status groups. Using a false discovery rate <0.05 and average group difference in DNAm ≥0.05, differentially methylated array sites were identified only in (1) the comparison of anencephaly to controls in chorionic villi (n = 4 sites) and (2) the comparison of spina bifida to controls in kidney (n = 3342 sites).
Conclusions
We suggest that the distinctive DNAm of spina bifida kidneys may be consequent to the neural tube defect or reflective of a common etiology for abnormal neural tube and renal development. Though there were some small shifts in DNAm in the other tested tissues, our data do not support the long-standing hypothesis of generalized altered genome-wide DNAm in NTDs. This finding may be related to the fact that most Canadians are not folate deficient, but it importantly opens the field to the investigation of other epigenetic and non-epigenetic mechanisms in the etiology of NTDs.
Electronic supplementary material
The online version of this article (doi:10.1186/s13072-016-0054-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s13072-016-0054-8
PMCID: PMC4756451  PMID: 26889207
Neural tube defects (NTDs); Spina bifida; Anencephaly; Illumina HumanMethylation450 BeadChip; 450k array; Epigenome-wide association study (EWAS); DNA methylation (DNAm)
7.  Sharing with More Caring: Coordinating and Improving the Ethical Governance of Data and Biomaterials Obtained from Children 
PLoS ONE  2015;10(7):e0130527.
Introduction
Research on complex health conditions such as neurodevelopmental disorders increasingly relies on large-scale research and clinical studies that would benefit from data sharing initiatives. Organizations that share data stand to maximize the efficiency of invested research dollars, expedite research findings, minimize the burden on the patient community, and increase citation rates of publications associated with the data.
Objective
This study examined ethics and governance information on websites of databases involving neurodevelopmental disorders to determine the availability of information on key factors crucial for comprehension of, and trust and participation in such initiatives.
Methods
We identified relevant databases identified using online keyword searches. Two researchers reviewed each of the websites and identified thematic content using principles from grounded theory. The content for each organization was interrogated using the gap analysis method.
Results
Sixteen websites from data sharing organizations met our inclusion criteria. Information about types of data and tissues stored, data access requirements and procedures, and protections for confidentiality were significantly addressed by data sharing organizations. However, special considerations for minors (absent from 63%), controls to check if data and tissues are being submitted (absent from 81%), disaster recovery plans (absent from 81%), and discussions of incidental findings (absent from 88%) emerged as major gaps in thematic website content. When present, content pertaining to special considerations for youth, along with other ethics guidelines and requirements, were scattered throughout the websites or available only from associated documents accessed through live links.
Conclusion
The complexities of sharing data acquired from children and adolescents will only increase with advances in genomic and neuro science. Our findings suggest that there is a need to improve the consistency, depth and accessibility of governance and policies on which these collaborations can lean specifically for vulnerable young populations.
doi:10.1371/journal.pone.0130527
PMCID: PMC4488593  PMID: 26132205
8.  Meta-analysis of human methylomes reveals stably methylated sequences surrounding CpG islands associated with high gene expression 
Background
DNA methylation is thought to play an important role in the regulation of mammalian gene expression, partly based on the observation that a lack of CpG island methylation in gene promoters is associated with high transcriptional activity. However, the CpG island methylation level only accounts for a fraction of the variance in gene expression, and methylation in other domains is hypothesized to play a role. We hypothesized that regions of very high stability in methylation would exist and provide biological insight into the role of methylation both within and outside CpG islands.
Results
We set out to identify highly stable regions in the human methylome, based on the subset of CpGs assayed with an Illumina Infinium 450 K array. Using 1,737 samples from 30 publically available studies, we identified 15,224 CpGs that are ‘ultrastable’ in their state across tissues and developmental stages (974 always methylated; 14,250 always unmethylated). Further analysis of ultrastable CpGs led us to identify a novel subset of CpG islands, ‘ravines’, which exhibit a markedly consistent pattern of low methylation with highly methylated flanking shores and shelves. We distinguish ravines from other CpG islands characterized by a broader flanking region of low methylation. Interestingly, ravines are associated with higher gene expression compared to typical unmethylated CpG islands, and are more often found near housekeeping genes.
Conclusions
The identification of ultrastable sites in the human methylome led us to identify a subclass of CpG islands characterized by a very stable pattern of methylation encompassing the island and flanking regions, established early in development and maintained through differentiation. This pattern is associated with particularly high levels of gene expression, providing new evidence that methylation beyond the CpG island could play a role in gene expression.
Electronic supplementary material
The online version of this article (doi:10.1186/1756-8935-7-28) contains supplementary material, which is available to authorized users.
doi:10.1186/1756-8935-7-28
PMCID: PMC4260796  PMID: 25493099
9.  Targeted CNS Delivery Using Human MiniPromoters and Demonstrated Compatibility with Adeno-Associated Viral Vectors 
Critical for human gene therapy is the availability of small promoter tools to drive gene expression in a highly specific and reproducible manner. We tackled this challenge by developing human DNA MiniPromoters using computational biology and phylogenetic conservation. MiniPromoters were tested in mouse as single-copy knock-ins at the Hprt locus on the X Chromosome, and evaluated for lacZ reporter expression in CNS and non-CNS tissue. Eighteen novel MiniPromoters driving expression in mouse brain were identified, two MiniPromoters for driving pan-neuronal expression, and 17 MiniPromoters for the mouse eye. Key areas of therapeutic interest were represented in this set: the cerebral cortex, embryonic hypothalamus, spinal cord, bipolar and ganglion cells of the retina, and skeletal muscle. We also demonstrated that three retinal ganglion cell MiniPromoters exhibit similar cell-type specificity when delivered via adeno-associated virus (AAV) vectors intravitreally. We conclude that our methodology and characterization has resulted in desirable expression characteristics that are intrinsic to the MiniPromoter, not dictated by copy number effects or genomic location, and results in constructs predisposed to success in AAV. These MiniPromoters are immediately applicable for pre-clinical studies towards gene therapy in humans, and are publicly available to facilitate basic and clinical research, and human gene therapy.
doi:10.1038/mtm.2013.5
PMCID: PMC3992516  PMID: 24761428
promoters; AAV; gene therapy
10.  Targeted CNS delivery using human MiniPromoters and demonstrated compatibility with adeno-associated viral vectors 
Critical for human gene therapy is the availability of small promoters tools to drive gene expression in a highly specific and reproducible manner. We tackled this challenge by developing human DNA MiniPromoters (MiniPs) using computational biology and phylogenetic conservation. MiniPs were tested in mouse as single-copy knock-ins at the Hprt locus on the X chromosome and evaluated for lacZ reporter expression in central nervous system (CNS) and non–CNS tissue. Eighteen novel MiniPs driving expression in mouse brain were identified, 2 MiniPs for driving pan-neuronal expression and 17 MiniPs for the mouse eye. Key areas of therapeutic interest were represented in this set: the cerebral cortex, embryonic hypothalamus, spinal cord, bipolar and ganglion cells of the retina, and skeletal muscle. We also demonstrated that three retinal ganglion cell MiniPs exhibit similar cell type specificity when delivered via adeno-associated virus vectors intravitreally. We conclude that our methodology and characterization has resulted in desirable expression characteristics that are intrinsic to the MiniPromoter, not dictated by copy-number effects or genomic location, and results in constructs predisposed to success in adeno-associated virus. These MiniPs are immediately applicable for preclinical studies toward gene therapy in humans and are publicly available to facilitate basic and clinical research, and human gene therapy.
doi:10.1038/mtm.2013.5
PMCID: PMC3992516  PMID: 24761428
11.  Non-coding-regulatory regions of human brain genes delineated by bacterial artificial chromosome knock-in mice 
BMC Biology  2013;11:106.
Background
The next big challenge in human genetics is understanding the 98% of the genome that comprises non-coding DNA. Hidden in this DNA are sequences critical for gene regulation, and new experimental strategies are needed to understand the functional role of gene-regulation sequences in health and disease. In this study, we build upon our HuGX ('high-throughput human genes on the X chromosome’) strategy to expand our understanding of human gene regulation in vivo.
Results
In all, ten human genes known to express in therapeutically important brain regions were chosen for study. For eight of these genes, human bacterial artificial chromosome clones were identified, retrofitted with a reporter, knocked single-copy into the Hprt locus in mouse embryonic stem cells, and mouse strains derived. Five of these human genes expressed in mouse, and all expressed in the adult brain region for which they were chosen. This defined the boundaries of the genomic DNA sufficient for brain expression, and refined our knowledge regarding the complexity of gene regulation. We also characterized for the first time the expression of human MAOA and NR2F2, two genes for which the mouse homologs have been extensively studied in the central nervous system (CNS), and AMOTL1 and NOV, for which roles in CNS have been unclear.
Conclusions
We have demonstrated the use of the HuGX strategy to functionally delineate non-coding-regulatory regions of therapeutically important human brain genes. Our results also show that a careful investigation, using publicly available resources and bioinformatics, can lead to accurate predictions of gene expression.
doi:10.1186/1741-7007-11-106
PMCID: PMC4015596  PMID: 24124870
Humanized mouse models; Brain expression pattern; Eye expression pattern; Brain development; Reporter gene; Transgenic mice; Hprt locus; High-throughput; Bacterial artificial chromosome
12.  Neurocarta: aggregating and sharing disease-gene relations for the neurosciences 
BMC Genomics  2013;14:129.
Background
Understanding the genetic basis of diseases is key to the development of better diagnoses and treatments. Unfortunately, only a small fraction of the existing data linking genes to phenotypes is available through online public resources and, when available, it is scattered across multiple access tools.
Description
Neurocarta is a knowledgebase that consolidates information on genes and phenotypes across multiple resources and allows tracking and exploring of the associations. The system enables automatic and manual curation of evidence supporting each association, as well as user-enabled entry of their own annotations. Phenotypes are recorded using controlled vocabularies such as the Disease Ontology to facilitate computational inference and linking to external data sources. The gene-to-phenotype associations are filtered by stringent criteria to focus on the annotations most likely to be relevant. Neurocarta is constantly growing and currently holds more than 30,000 lines of evidence linking over 7,000 genes to 2,000 different phenotypes.
Conclusions
Neurocarta is a one-stop shop for researchers looking for candidate genes for any disorder of interest. In Neurocarta, they can review the evidence linking genes to phenotypes and filter out the evidence they’re not interested in. In addition, researchers can enter their own annotations from their experiments and analyze them in the context of existing public annotations. Neurocarta’s in-depth annotation of neurodevelopmental disorders makes it a unique resource for neuroscientists working on brain development.
doi:10.1186/1471-2164-14-129
PMCID: PMC3599981  PMID: 23442263
Phenotype; Genes; Knowledgebase; Brain development
13.  The Transcription Factor Encyclopedia 
Yusuf, Dimas | Butland, Stefanie L | Swanson, Magdalena I | Bolotin, Eugene | Ticoll, Amy | Cheung, Warren A | Cindy Zhang, Xiao Yu | Dickman, Christopher TD | Fulton, Debra L | Lim, Jonathan S | Schnabl, Jake M | Ramos, Oscar HP | Vasseur-Cognet, Mireille | de Leeuw, Charles N | Simpson, Elizabeth M | Ryffel, Gerhart U | Lam, Eric W-F | Kist, Ralf | Wilson, Miranda SC | Marco-Ferreres, Raquel | Brosens, Jan J | Beccari, Leonardo L | Bovolenta, Paola | Benayoun, Bérénice A | Monteiro, Lara J | Schwenen, Helma DC | Grontved, Lars | Wederell, Elizabeth | Mandrup, Susanne | Veitia, Reiner A | Chakravarthy, Harini | Hoodless, Pamela A | Mancarelli, M Michela | Torbett, Bruce E | Banham, Alison H | Reddy, Sekhar P | Cullum, Rebecca L | Liedtke, Michaela | Tschan, Mario P | Vaz, Michelle | Rizzino, Angie | Zannini, Mariastella | Frietze, Seth | Farnham, Peggy J | Eijkelenboom, Astrid | Brown, Philip J | Laperrière, David | Leprince, Dominique | de Cristofaro, Tiziana | Prince, Kelly L | Putker, Marrit | del Peso, Luis | Camenisch, Gieri | Wenger, Roland H | Mikula, Michal | Rozendaal, Marieke | Mader, Sylvie | Ostrowski, Jerzy | Rhodes, Simon J | Van Rechem, Capucine | Boulay, Gaylor | Olechnowicz, Sam WZ | Breslin, Mary B | Lan, Michael S | Nanan, Kyster K | Wegner, Michael | Hou, Juan | Mullen, Rachel D | Colvin, Stephanie C | Noy, Peter John | Webb, Carol F | Witek, Matthew E | Ferrell, Scott | Daniel, Juliet M | Park, Jason | Waldman, Scott A | Peet, Daniel J | Taggart, Michael | Jayaraman, Padma-Sheela | Karrich, Julien J | Blom, Bianca | Vesuna, Farhad | O'Geen, Henriette | Sun, Yunfu | Gronostajski, Richard M | Woodcroft, Mark W | Hough, Margaret R | Chen, Edwin | Europe-Finner, G Nicholas | Karolczak-Bayatti, Magdalena | Bailey, Jarrod | Hankinson, Oliver | Raman, Venu | LeBrun, David P | Biswal, Shyam | Harvey, Christopher J | DeBruyne, Jason P | Hogenesch, John B | Hevner, Robert F | Héligon, Christophe | Luo, Xin M | Blank, Marissa Cathleen | Millen, Kathleen Joyce | Sharlin, David S | Forrest, Douglas | Dahlman-Wright, Karin | Zhao, Chunyan | Mishima, Yuriko | Sinha, Satrajit | Chakrabarti, Rumela | Portales-Casamar, Elodie | Sladek, Frances M | Bradley, Philip H | Wasserman, Wyeth W
Genome Biology  2012;13(3):R24.
Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.
doi:10.1186/gb-2012-13-3-r24
PMCID: PMC3439975  PMID: 22458515
14.  MIR@NT@N: a framework integrating transcription factors, microRNAs and their targets to identify sub-network motifs in a meta-regulation network model 
BMC Bioinformatics  2011;12:67.
Background
To understand biological processes and diseases, it is crucial to unravel the concerted interplay of transcription factors (TFs), microRNAs (miRNAs) and their targets within regulatory networks and fundamental sub-networks. An integrative computational resource generating a comprehensive view of these regulatory molecular interactions at a genome-wide scale would be of great interest to biologists, but is not available to date.
Results
To identify and analyze molecular interaction networks, we developed MIR@NT@N, an integrative approach based on a meta-regulation network model and a large-scale database. MIR@NT@N uses a graph-based approach to predict novel molecular actors across multiple regulatory processes (i.e. TFs acting on protein-coding or miRNA genes, or miRNAs acting on messenger RNAs). Exploiting these predictions, the user can generate networks and further analyze them to identify sub-networks, including motifs such as feedback and feedforward loops (FBL and FFL). In addition, networks can be built from lists of molecular actors with an a priori role in a given biological process to predict novel and unanticipated interactions. Analyses can be contextualized and filtered by integrating additional information such as microarray expression data. All results, including generated graphs, can be visualized, saved and exported into various formats. MIR@NT@N performances have been evaluated using published data and then applied to the regulatory program underlying epithelium to mesenchyme transition (EMT), an evolutionary-conserved process which is implicated in embryonic development and disease.
Conclusions
MIR@NT@N is an effective computational approach to identify novel molecular regulations and to predict gene regulatory networks and sub-networks including conserved motifs within a given biological context. Taking advantage of the M@IA environment, MIR@NT@N is a user-friendly web resource freely available at http://mironton.uni.lu which will be updated on a regular basis.
doi:10.1186/1471-2105-12-67
PMCID: PMC3061897  PMID: 21375730
15.  Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis 
Nucleic Acids Research  2010;38(17):5718-5734.
The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response.
doi:10.1093/nar/gkq212
PMCID: PMC2943601  PMID: 20460467
16.  JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles 
Nucleic Acids Research  2009;38(Database issue):D105-D110.
JASPAR (http://jaspar.genereg.net) is the leading open-access database of matrix profiles describing the DNA-binding patterns of transcription factors (TFs) and other proteins interacting with DNA in a sequence-specific manner. Its fourth major release is the largest expansion of the core database to date: the database now holds 457 non-redundant, curated profiles. The new entries include the first batch of profiles derived from ChIP-seq and ChIP-chip whole-genome binding experiments, and 177 yeast TF binding profiles. The introduction of a yeast division brings the convenience of JASPAR to an active research community. As binding models are refined by newer data, the JASPAR database now uses versioning of matrices: in this release, 12% of the older models were updated to improved versions. Classification of TF families has been improved by adopting a new DNA-binding domain nomenclature. A curated catalog of mammalian TFs is provided, extending the use of the JASPAR profiles to additional TFs belonging to the same structural family. The changes in the database set the system ready for more rapid acquisition of new high-throughput data sources. Additionally, three new special collections provide matrix profile data produced by recent alternative high-throughput approaches.
doi:10.1093/nar/gkp950
PMCID: PMC2808906  PMID: 19906716
17.  The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences 
Nucleic Acids Research  2008;37(Database issue):D54-D60.
The PAZAR database unites independently created and maintained data collections of transcription factor and regulatory sequence annotation. The flexible PAZAR schema permits the representation of diverse information derived from experiments ranging from biochemical protein–DNA binding to cellular reporter gene assays. Data collections can be made available to the public, or restricted to specific system users. The data ‘boutiques’ within the shopping-mall-inspired system facilitate the analysis of genomics data and the creation of predictive models of gene regulation. Since its initial release, PAZAR has grown in terms of data, features and through the addition of an associated package of software tools called the ORCA toolkit (ORCAtk). ORCAtk allows users to rapidly develop analyses based on the information stored in the PAZAR system. PAZAR is available at http://www.pazar.info. ORCAtk can be accessed through convenient buttons located in the PAZAR pages or via our website at http://www.cisreg.ca/ORCAtk.
doi:10.1093/nar/gkn783
PMCID: PMC2686574  PMID: 18971253
18.  Identification of a set of genes showing regionally enriched expression in the mouse brain 
BMC Neuroscience  2008;9:66.
Background
The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain.
Results
We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology.
Conclusion
Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.
doi:10.1186/1471-2202-9-66
PMCID: PMC2483290  PMID: 18625066
19.  ORegAnno: an open-access community-driven resource for regulatory annotation 
Nucleic Acids Research  2007;36(Database issue):D107-D113.
ORegAnno is an open-source, open-access database and literature curation system for community-based annotation of experimentally identified DNA regulatory regions, transcription factor binding sites and regulatory variants. The current release comprises 30 145 records curated from 922 publications and describing regulatory sequences for over 3853 genes and 465 transcription factors from 19 species. A new feature called the ‘publication queue’ allows users to input relevant papers from scientific literature as targets for annotation. The queue contains 4438 gene regulation papers entered by experts and another 54 351 identified by text-mining methods. Users can enter or ‘check out’ papers from the queue for manual curation using a series of user-friendly annotation pages. A typical record entry consists of species, sequence type, sequence, target gene, binding factor, experimental outcome and one or more lines of experimental evidence. An evidence ontology was developed to describe and categorize these experiments. Records are cross-referenced to Ensembl or Entrez gene identifiers, PubMed and dbSNP and can be visualized in the Ensembl or UCSC genome browsers. All data are freely available through search pages, XML data dumps or web services at: http://www.oreganno.org.
doi:10.1093/nar/gkm967
PMCID: PMC2239002  PMID: 18006570
20.  PAZAR: a framework for collection and dissemination of cis-regulatory sequence annotation 
Genome Biology  2007;8(10):R207.
PAZAR is an open-access and open-source database of transcription factor and regulatory sequence annotation with associated web interface and programming tools for data submission and extraction.
PAZAR is an open-access and open-source database of transcription factor and regulatory sequence annotation with associated web interface and programming tools for data submission and extraction. Curated boutique data collections can be maintained and disseminated through the unified schema of the mall-like PAZAR repository. The Pleiades Promoter Project collection of brain-linked regulatory sequences is introduced to demonstrate the depth of annotation possible within PAZAR. PAZAR, located at , is open for business.
doi:10.1186/gb-2007-8-10-r207
PMCID: PMC2246282  PMID: 17916232
21.  M-Cadherin Activates Rac1 GTPase through the Rho-GEF Trio during Myoblast Fusion 
Molecular Biology of the Cell  2007;18(5):1734-1743.
Cadherins are transmembrane glycoproteins that mediate Ca2+-dependent homophilic cell–cell adhesion and play crucial role during skeletal myogenesis. M-cadherin is required for myoblast fusion into myotubes, but its mechanisms of action remain unknown. The goal of this study was to cast some light on the nature of the M-cadherin–mediated signals involved in myoblast fusion into myotubes. We found that the Rac1 GTPase activity is increased at the time of myoblast fusion and it is required for this process. Moreover, we showed that M-cadherin–dependent adhesion activates Rac1 and demonstrated the formation of a multiproteic complex containing M-cadherin, the Rho-GEF Trio, and Rac1 at the onset of myoblast fusion. Interestingly, Trio knockdown efficiently blocked both the increase in Rac1-GTP levels, observed after M-cadherin–dependent contact formation, and myoblast fusion. We conclude that M-cadherin–dependent adhesion can activate Rac1 via the Rho-GEF Trio at the time of myoblast fusion.
doi:10.1091/mbc.E06-08-0766
PMCID: PMC1855016  PMID: 17332503

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