Strengthening insights into host responses to mastitis infection in ruminants by combining heterogeneous microarray data sources
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* Corresponding author: Sem Genini geninis@vet.upenn.edu
- Equal contributors
1 Parco Tecnologico Padano - CERSA, Via Einstein, 26900 Lodi, Italy
2 The Roslin Institute and R(D)SVS, Division of Genetics and Genomics, Roslin, Midlothian, University of Edinburgh, EH25 9RG, UK
3 INRA/AgroParisTech, UMR1236 Génétique et Diversité Animales, F-78352 Jouy en Josas, France
4 INRA, Sigenae UR875 Biométrie et Intelligence Artificielle, BP 52627, F-31326 Castanet-Tolosan Cedex, France
5 INRA, Sigenae UR83 Recherches Avicoles, F-37380 Nouzilly, France
6 Leibniz Institute for Farm Animal Biology (FBN), Molecular Biology Research Unit, Wilhelm-Stahl-Allee 2, D-18196 Dummerstorf, Germany
7 Clinic for Ruminants, Ludwig-Maximilians University, Munich, Germany
8 Central Veterinary Institute of Wageningen UR, P.O. Box 65, 8200 AB, Lelystad, The Netherlands
9 Wageningen UR Livestock Research, Animal Breeding and Genomics Centre, P.O. Box 65, 8200 AB, Lelystad, The Netherlands
10 Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, P.O. Box 8146 Dep, NO-0033 Oslo, Norway
11 Università degli Studi di Milano, Department of Veterinary Pathology, Hygiene and Public Health, via Celoria 10, 20133 Milan, Italy
12 Istituto di Biologia e Biotecnologia Agraria, Consiglio Nazionale delle Ricerche, Milan, Italy
13 INRA-ENVT, UMR1225, Interactions Hôtes Agents Pathogènes, F-31300 Toulouse, France
14 INRA, UR631, Station d'Amélioration Génétique des Animaux, F-31326 Castanet-Tolosan, France
15 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
16 Quality Milk Production Services, Cornell University, Ithaca, New York, USA
17 INRA, UMR 1313 de Génétique Animale et Biologie Intégrative, Jouy-en-Josas, France
BMC Genomics 2011, 12:225 doi:10.1186/1471-2164-12-225
Published: 11 May 2011Additional files
Additional file 1:
Lists of affected genes during different responses to mastitis infection. Complete lists of affected genes and corresponding "Combined Effective Significances (CES)" identified with pointillist for the 4 main responses to mastitis (I) overall response, (II) early stage response, (III) late stage response, (IV) cattle-specific response, as well as the two additional time dependent responses (V) early specific and (VI) late specific.
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Additional file 2:
Lists of all affected canonical pathways and corresponding affected genes. Complete lists of affected canonical pathways (p < 0.05) and corresponding affected genes identified with IPA for the meta-analysis combinations (I) overall response, (II) early stage response, (III) late stage response, (IV) cattle-specific response, (V) early specific response and (VI) late specific response, as well as for the common affected genes between the 4 meta-analysis responses (I) to (IV) (Figure 3, n = 92). The identified canonical pathways are listed from the lowest to the highest p-value. An asterisk indicates that the pathway approached statistical significance (0.05<p < 0.1).
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Additional file 3:
Lists of all affected biological functions and corresponding affected genes. Complete lists of all affected biological functions (p < 0.05) and corresponding affected genes identified with IPA for the meta-analysis combinations (I) overall response, (II) early stage response, (III) late stage response, (IV) cattle-specific response, (V) early specific response and (VI) late specific response, as well as for the common affected genes between the 4 meta-analysis responses (I) to (IV) (Figure 3, n = 92). The biological functions include all the sub-groups "Diseases and disorders", "Physiological system development and function" and "Molecular and cellular functions" and are listed from the lowest to the highest p-value. The five most affected molecular and cellular functions, which are discussed in the text, are in bold.
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Additional file 4:
Affected sub-functions of lipid metabolism during different responses to mastitis infection. Five most significant sub-functions of lipid metabolism that are altered during (I) overall, (II) early stage, (III) late stage, and (IV) cattle-specific responses. The results were obtained by IPA using the lists of significantly affected genes for each specific response. The sub-functions of the lipid metabolism are listed from the lowest to the highest p-value, and are reported with the involved genes.
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Additional file 5:
Supplemental Figure S1 - Relationship between XBP1 and additional affected genes during the early stage response to mastitis. Gene network showing the connections, as identified with the IPA option "building pathways", between the gene XBP1 and other affected genes during (II) early stage response to mastitis infection. A. XBP1 is related and linked to several other affected genes. B. XBP1 is directly linked to the genes COPZ1, DDOST, KDELR2, KDELR3, RPN1, SEC23B, SEC24D, SEC61A1, and SRPR, as well as to genes of the proteasome and the MHC Class II complex. Supplemental Figure S2 - Relationship between SREBF1 and additional affected genes during the late stage response to mastitis. Gene network showing the connections, as identified with the IPA option "building pathways", between affected genes involved in lipid metabolism during (III) late stage response to mastitis infection. The gene SREBF1 seems to play an important role and is directly linked to other affected genes (violet colour), i.e. TRAF3IP3, CD36, SCD, SOD1, IDH1, THRB, RETN, PMVK, DBI, UCP2, HBS1, SC4MOL, and CYP27A1. Supplemental Figure S3 - Venn diagram showing the number of common and experiment-specific affected genes between (IV) cattle-specific response and the individual experiments 1A time point {3} and 2 time point {9}. Venn diagram illustrating the number of significantly affected genes in common (25) and distinct for the (IV) cattle-specific response (red: 421 genes), experiment 1A time point {3} (green: 745 genes), and experiment 2 time point {9} (blue: 55 genes). The lists of corresponding genes can be found in [Additional file 6]. The list of experiments and time points can be found in Table 1 and the list of meta-analysis combinations in Table 2.
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Additional file 6:
Lists of affected genes that are distinct or in common between (IV) cattle-specific response, experiment 1A time point {3}, and experiment 2 time point {9}. Complete lists of affected genes corresponding to the Venn diagram [Additional file 5: Supplemental Figure S3], including genes that are distinct or in common at the intersections between (IV) cattle-specific response, experiment 1A time point {3}, and experiment 2 time point {9}. The list of experiments and time points can be found in Table 1 and the list of meta-analysis combinations in Table 2.
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Additional file 7:
Affected molecular and cellular functions of the most dissimilar genes between E. coli and S. aureus. Five most significant molecular and cellular functions identified with IPA using the 34 most dissimilar genes between E. coli and S. aureus infections in cattle in vivo (experiment 1A, 1B, and 1C), as found with the PAMR software (Table 3). The identified molecular and cellular functions are listed from the lowest to the highest p-value, and are reported with the involved genes.
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Additional file 8:
Lists of affected genes that are distinct or in common between the 4 main responses to mastitis infection. Complete lists of affected genes corresponding to the Venn diagram in Figure 3, including genes that are distinct or in common at the intersections between the 4 different responses (I) overall, (II) early stage, (III) late stage, and (IV) cattle-specific.
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