611:. You must enter a protein sequence in the first box and the substitutions relative to this protein sequence in the second box; this substitutions should be entered in the standard amino acid substitution format, e.g. L46P. PANTHER will use an alignment of evolutionarily related proteins, calculate the substitution position-specific evolutionary conservation (subPSEC) and estimate the
455:
probes. PANTHER version 7 uses the SBGN standard to depict biological pathways. It includes 48 set of genomes. To define the new families and in collaboration with the
European Bioinformatics Institute’s InterPro group, approximately 1000 families of non-animal genomes were added in this version. The
472:
The reference proteome set maintained by the UniProt resource is used in this version of PANTHER and so the source of gene sets is UniProt. It includes 82 set of genomes (approximately double compared with version 7) and 991985 protein coding genes from which 642319 genes (64.75%) have been used for
358:
Each node in PANTHER tree is annotated with heritable attribute. Heritable attribute can be of three types subfamily membership, gene function and protein class membership. These annotation of nodes applies to primary sequence which was used to construct tree. In applying these annotation to primary
245:
Each node is annotated by gene attributes including “subfamily membership”, “protein class”, “gene function”. These attributes are heritable. Swiss-Prot protein names are usually used to name subfamilies. Since PANTHER is part of the GO reference genome project, the Gene
Ontology (GO) terms are used
624:
Entering a search term in the keyword search box, PANTHER will give you the number of records matching your keyword for genes, families, pathways and ontology terms. You can filter them by determining the species of interest or by refining the search using other criteria. To view the details of the
513:
Let's try this workflow using an example of a small gene list containing three genes AKT1, AKT2, AKT3. We first type these gene names within the box and separate them by comma (or space). We select "ID list" as list type, "Homo
Sapiens" (human) as organism, and " Functional classification viewed in
298:
PANTHER trees depicts gene family evolution from a broad selection of genomes which are fully sequenced. PANTHER have one sequence per gene so that the tree can represent event occurred over the course of evolution i.e duplication, speciation. PANTHER genomes set are selected based on the following
434:
Version 6 uses UniProt sequences as training sequences. There are 19132 UniProt training sequences directly associated with the pathway components. This version has ~1500 reactions in 130 pathways, and the number of pathways associated with subfamilies were expanded. PANTHER became a member of the
589:
Using this folder tab and by selecting the ontology you are interested in, you can browse different classification. It is also possible to select more than one ontology; in this case, the results will meet the criteria from all the selections. You are able to see the association between ontology
598:
By putting the protein sequence in the
Sequence Search box, PANTHER will search against a library of family and subfamily HMMs, and return the subfamily that best matches the sequence. If you click on the subfamily name, it will give some details, e.g. the genes related to that subfamily and the
615:
of this nonsynonymous coding SNP to lead a functional effect on the protein. This tool uses data from PANTHER version 6.1 for technical reasons. One of the new features of PANTHER is that if you want to analyze a lot of SNPs, you can go to the download page and download the PANTHER Coding Snp
540:
This will give you the name of family and subfamily for your genes. There are some links, e.g. a link to the family tree, which is clickable. Finally you will have the genes from different species assigned to that subfamily. In this example you have the PANTHER subfamily "PTHR24352:SF30" for
144:
The project consists of both manual curation and bioinformatics algorithms. Proteins are classified according to family (and subfamily), molecular function, biological process and pathway. It is one of the databases feeding into the
European Bioinformatics Institute's
350:, any column which is aligned less than 75% of the sequence is removed. This data is then used as an input for GIGA program. The output tree from GIGA are labelled. Each internal node is labelled as whether divergence event happened as speciation or gene duplication.
149:
database.—Application of PANTHER—The most important application of PANTHER is to accurately infer the function of uncharacterized genes from any organism based on their evolutionary relationships to genes with known functions. By combining gene function,
559:
It tells you where in the cell you can find your query protein. In our example, the information is not available but if you try another examples (such as the gene p53), you will see some cellular components such as "nucleus", "cytoplasm", "chromosomes",
533:
the orthologs are clickable and by clicking on them you can see the list of other organisms and their IDs as well as the type of orthologs ("LDO" for least diverged ortholog, "O" for other which are more diverged orthologs, and "P" for
566:
this gives you the names and IDs of PANTHER protein class for each of the genes; e.g. AKT1 is under PANTHER protein class "non-receptor serine/threonine protein kinase" with class ID "PC00167". You can also see its parent and child
497:
The home page of PANTHER website shows several folder tabs for major workflows, including: gene list analysis, browse, sequence search, cSNP scoring, and keyword search. The details about each of these workflow are provided below.
133:) classification system is a large curated biological database of gene/protein families and their functionally related subfamilies that can be used to classify and identify the function of gene products. PANTHER is part of the
573:
A list of clickable names of the pathways in which your query gene exists will be shown; e.g. AKT1 is involved in several pathways such as "Hypoxia response via HIF", "Apoptosis signaling pathway", "PI3 kinase pathway",
506:
This tab is selected by default because this the most frequently used option. You can enter valid IDs in the box or upload a file, then select list type, choose organism of interest and select the type of analysis.
265:
To generate phylogenetic trees, PANTHER uses GIGA algorithm. GIGA uses species tree to develop tree construction. On every iteration it attempts to reconcile tree in event form of speciation and gene duplication.
392:
and so when it is biologically justified, child categories appear under more than one parent. PANTHER/X has been mapped to GO and arranged in a different way to facilitate large scale analysis of proteins.
547:
This tell you what are the functions of your query gene; e.g. AKT1 has protein kinase activity and can selectively and non-covalently interact with calcium ions, calmodulin, and phospholipids.
464:
Gene. Since this version, a stable identifier to each node in the tree is used. This stable identifier is a nine-digit number with the prefix PTN (stand for PANTHER Tree Node). (2009)
599:
ability to view the subfamily within larger family tree. By downloading the PANTHER scoring tool from download page, you will be able to score many sequences against PANTHER HMMs.
154:, pathways and statistical analysis tools, PANTHER enables biologists to analyze large-scale, genome-wide data obtained from the current advance technology including: sequencing,
553:
By looking at this column, you will understand what biological processes the gene involved in; e.g. AKT1 has role in gamete generation, apoptosis, cell cycle, etc.
337:
The assessment of multiple aligned sequence is done by assessing a length of the aligned sequence, at least 30 sites aligned across 75% or more of family members.
481:
This version contains 7180 protein families, divided into 52,768 functionally distinct protein subfamilies. Version 9.0 has genomes of all 85 organisms.
384:
Index contains abbreviated ontology which assist in summarizing, navigating molecular function and biological function. Although PANTHER/X ontology has a
439:). The PANTHER/LIB version 6.1 contains 221609 UniProt sequences from 53 organisms, grouped into 5546 families and 24561 subfamilies. (2006)
648:"PANTHER: a browsable database of gene products organized by biological function, using curated protein family and subfamily classification"
412:
62:
646:
Thomas, PD.; Kejariwal, A.; Campbell, MJ.; Mi, H.; Diemer, K.; Guo, N.; Ladunga, I.; Ulitsky-Lazareva, B.; et al. (Jan 2003).
1092:
Wu, C.H.; Apweiler, R.; Bairoch, A.; Natale, D.A.; Barker, W.C.; Boeckmann, B.; Ferro, S.; Gasteiger, E.; et al. (Jan 2006).
779:
Hunter, S.; Jones, P.; Mitchell, A.; Apweiler, R.; Attwood, TK.; Bateman, A.; Bernard, T.; Binns, D.; et al. (Jan 2012).
898:"PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements"
729:"PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees"
314:
range of other genomes, preferably fully sequenced and annotated, this will assist in relating experimental model organism.
172:
Create lists of genes related to a particular protein family/subfamily, molecular function, biological process or pathway.
514:
gene list" as the type of operation; then click submit. It gives you the information for all the three genes which are:
401:
PANTHER includes 176 pathway using CellDesigner tool. PANTHER pathways can be downloaded in the following file formats.
169:
Discover protein families and subfamilies, pathways, biological processes, molecular functions and cellular components.
1372:
1190:
Flicek, P.; Amode, M.R.; Barrell, D.; Beal, K.; Brent, S.; Chen, Y.; Clapham, P.; Coates, G.; et al. (Jan 2011).
375:
1143:"PANTHER version 6: protein sequence and function evolution data with expanded representation of biological pathways"
327:
The family must contain at least five members among which at least one gene has to be from a GO reference genome.
138:
447:
In this version the phylogenetic trees represent speciation and gene duplication events. Identification of gene
1293:"PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium"
258:
17:
698:
359:
sequence simple evolutionary principle is used i.e. each node annotation is propagated by its decedent node.
389:
207:
2005: PANTHER 5 released with PANTHER Pathway and analysis tool. Establish collaboration with InterPro.
194:
2001: PANTHER 2 released, which is used in the annotationon of the first published human genome Celera.
370:
Library consists of collection of books. Each of these books represents a protein family. There are a
371:
527:
these are simply the names of the genes which have been mapped to your query (AKT1, AKT2 and AKT3)
435:
InterPro
Consortium. The availability of PANTHER data was improved (the HMMs can be downloaded by
241:
for each of the protein families. The annotation of tree is done based on the following criteria:
451:
is possible. There are more support for alternative database identifiers for genes, proteins and
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996:"Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium"
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307:, this will assist in depicting functional information of the organism which are less studied.
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Mi, H; Huang, X; Muruganujan, A; Tang, H; Mills, C; Kang, D; Thomas, PD (29 November 2016).
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1094:"The Universal Protein Resource (UniProt): an expanding universe of protein information"
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experiments. Shortly, using the data and tools on the PANTHER, users will be able to:
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134:
1354:
1291:
Mi, H.; Dong, Q.; Muruganujan, A.; Gaudet, P.; Lewis, S.; Thomas, P.D. (Jan 2010).
473:
family clusters. PANTHER website is redesigned to facilitate common user workflow.
385:
330:
In order to support phylogenetic inference, the family must contain a high quality
580:
This is the name of species you have chosen; in this case we chose "Homo sapiens".
204:
2003: PANTHER 4 released with the public release of PANTHER Classification System.
781:"InterPro in 2011: new developments in the family and domain prediction database"
612:
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155:
1340:
947:"Reorganizing the protein space at the Universal Protein Resource (UniProt)"
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830:"Large-scale gene function analysis with the PANTHER classification system"
814:
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137:
Reference Genome
Project designed to classify proteins and their genes for
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For each family multiple sequence are aligned using a default setting of
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Using this folder tab, you are able to do evolution analysis of coding
489:
This version contains 78442 subfamilies and 1,064,054 genes annotated.
457:
246:
for gene function. PANTHER/X ontology terms are used for protein class.
198:
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in terms of this example, you must see "ENSG00000142208" and "P31749".
461:
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323:
Following are the requirements for being family clusters in PANTHER:
994:
Gaudet, P.; Livstone, M.S.; Lewis, S.E.; Thomas, P.D. (Sep 2011).
347:
608:
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terms and PANTHER families, subfamilies and training sequences.
406:
378:(MSA) and a family tree for each protein family in the library.
249:
Each internal node is annotated by evolutionary events such as “
197:
2002: PANTHER 3 released. PANTHER annotations are integrated in
436:
274:
The process for data generation is divided into three steps:
882:
99:
425:
Recent versions of PANTHER and their statistics and updates
37:
The PANTHER database classifies gene products into families
191:
2000:PANTHER 1 released in Celera
Discovery Systems (CDS).
185:
1998:Project was launched at
Molecular Application Group.
456:
sources of gene sets included model organism databases,
166:
Obtain information about a particular gene of interest.
1242:; Ostell, J.; Pruitt, K.D.; Tatusova, T. (Jan 2011).
1353:
Details in PANTHER 9 statistics can be found here (
519:
Gene IDs from
Ensembl and protein IDs from Uniprot:
131:
protein analysis through evolutionary relationships
109:
104:
95:
90:
76:
68:
56:
51:
41:
33:
28:
1355:http://www.pantherdb.org/panther/summaryStats.jsp
828:Mi, H.; Muruganujan, A.; Thomas, PD. (Aug 2013).
727:Mi, H.; Muruganujan, A.; Thomas, PD. (Jan 2013).
1244:"Entrez Gene: gene-centered information at NCBI"
175:Analyze lists of genes, proteins or transcripts.
774:
772:
641:
639:
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625:gene, you must click on the gene identifier.
8:
531:Gene names, gene symbols, and the orthologs:
303:The set should include a major experimental
23:
693:
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1141:Mi, H.; Guo, N.; Thomas, P.D. (Jan 2007).
1045:"The Gene Ontology: enhancements for 2011"
22:
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699:"GO Reference Genome Annotation Project"
633:
270:PANTHER library data generation process
210:2006: PANTHER 6 released. Move to SRI.
1043:Gene Ontology Consortium (Jan 2012).
7:
945:The UniProt Consortium (Jan 2012).
413:Systems Biology Graphical Notation
14:
405:Systems Biology Markup Language (
188:1999:Acquired by Celera Genomics.
63:University of Southern California
310:The set should include a broad
368:PANTHER/LIB (PANTHER library):
1:
1303:(Database issue): D204–D210.
1202:(Database issue): D800–D806.
1153:(Database issue): D247–D252.
1104:(Database issue): D187–D191.
538:PANTHER family and subfamily:
1254:(Database issue): D52–D57.
791:(Database issue): D306–12.
739:(Database issue): D377–86.
376:multiple sequence alignment
281:Pythologentic tree building
1389:
382:PANTHER/X (PANTEHR index):
342:Phylogenetic tree building
228:2016: PANTHER 11 released.
225:2015: PANTHER 10 released.
15:
222:2014: PANTHER 9 released.
219:2012: PANTHER 8 released.
213:2010: PANTHER 7 released.
354:Annotation of tree nodes
284:Annotation of tree nodes
259:horizontal gene transfer
18:Panther (disambiguation)
388:organization, it is a
902:Nucleic Acids Research
846:10.1038/nprot.2013.092
564:PANTHER protein class:
557:GO cellular component:
551:GO biological process:
545:GO molecular function:
460:genome annotation and
390:directed acyclic graph
237:In PANTHER there is a
1341:"reference proteome"
511:A practical example:
16:For other uses, see
1309:10.1093/nar/gkp1019
1260:10.1093/nar/gkq1237
1208:10.1093/nar/gkq1064
1061:10.1093/nar/gkr1028
914:10.1093/nar/gkw1138
745:10.1093/nar/gks1118
485:Version 11.1 (2016)
372:Hidden Markov Model
25:
1373:Genetics databases
1159:10.1093/nar/gkl869
1110:10.1093/nar/gkj161
1012:10.1093/bib/bbr042
963:10.1093/nar/gkr981
797:10.1093/nar/gkr948
664:10.1093/nar/gkg115
502:Gene list analysis
477:Version 9.0 (2014)
468:Version 8.0 (2012)
363:PANTHER components
332:sequence alignment
216:2011: Move to USC.
1297:Nucleic Acids Res
1248:Nucleic Acids Res
1196:Nucleic Acids Res
1147:Nucleic Acids Res
1098:Nucleic Acids Res
1055:(D1): D559–D564.
1049:Nucleic Acids Res
951:Nucleic Acids Res
908:(D1): D183–D189.
834:Nucleic Acids Res
785:Nucleic Acids Res
733:Nucleic Acids Res
652:Nucleic Acids Res
289:Family clustering
278:Family clustering
239:phylogenetic tree
233:Phylogenetic tree
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397:PANTHER pathways
255:gene duplication
77:Primary citation
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1000:Brief Bioinform
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957:(D1): D71–D75.
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616:Analysis tool.
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594:Sequence search
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493:PANTHER website
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319:Family clusters
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201:. Moved to ABI.
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180:PANTHER history
160:gene expression
139:high-throughput
111:
58:Research center
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12:
11:
5:
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888:
869:
840:(8): 1551–66.
820:
768:
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632:
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620:Keyword search
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1006:(5): 449–62.
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658:(1): 334–41.
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135:Gene Ontology
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294:Sequence set
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110:Bookmarkable
1240:Maglott, D.
883:"PANTHERdb"
525:Mapped IDs:
443:Version 7.0
430:Version 6.0
415:(SBGN - ML)
34:Description
629:References
613:likelihood
534:paralogs).
453:microarray
299:criteria:
251:speciation
156:proteomics
141:analysis.
42:Data types
1192:"Ensembl"
571:Pathways:
449:orthologs
374:(HMM), a
312:taxonomic
1367:Category
1327:20015972
1278:21115458
1226:21045057
1177:17130144
1128:16381842
1079:22102568
1030:21873635
981:22102590
932:27899595
864:23868073
815:22096229
763:23193289
682:12520017
578:Species:
567:lineage.
152:ontology
147:InterPro
112:entities
85:12520017
44:captured
1318:2808919
1269:3013746
1217:3013672
1168:1716723
1119:1347523
1070:3245151
1021:3178059
972:3245120
923:5210595
855:6519453
806:3245097
754:3531194
458:Ensembl
257:” and “
199:FlyBase
127:PANTHER
96:Website
69:Authors
52:Contact
29:Content
24:PANTHER
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541:AKT1.
348:MAFFT
1323:PMID
1274:PMID
1222:PMID
1173:PMID
1124:PMID
1075:PMID
1026:PMID
977:PMID
928:PMID
860:PMID
811:PMID
759:PMID
678:PMID
609:SNPs
574:etc.
560:etc.
407:SBML
253:”, “
81:PMID
1313:PMC
1305:doi
1264:PMC
1256:doi
1212:PMC
1204:doi
1163:PMC
1155:doi
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1106:doi
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