Limits...
Leveraging family-specific signatures for AMP discovery and high-throughput annotation.

Waghu FH, Barai RS, Idicula-Thomas S - Sci Rep (2016)

Bottom Line: As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance.The webserver is available online at www.campsign.bicnirrh.res.in.In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Informatics Centre of Indian Council of Medical Research, National Institute for Research in Reproductive Health, Mumbai-400012, India.

ABSTRACT
Antimicrobial peptides (AMPs) are diverse, biologically active, essential components of the innate immune system. As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance. They are widely researched for their therapeutic potential, especially against multi-drug resistant pathogens. AMPs are known to have family-specific sequence composition, which can be mined for their discovery and rational design. Here, we present a detailed family-based study on AMP families. The study involved the use of sequence signatures represented by patterns and hidden Markov models (HMMs) present in experimentally studied AMPs to identify novel AMPs. Along with AMPs, peptides hitherto lacking antimicrobial annotation were also retrieved and wet-lab studies on randomly selected sequences proved their antimicrobial activity against Escherichia coli. CAMPSign, a webserver has been created for researchers to effortlessly exploit the use of AMP family signatures for identification of AMPs. The webserver is available online at www.campsign.bicnirrh.res.in. In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

No MeSH data available.


Related in: MedlinePlus

(a) Venn diagram of sequences retrieved using patterns and HMMs. (b) Venn diagram of sequences retrieved using length-based HMMs and HMMs created using sequences with undefined length.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4836297&req=5

f1: (a) Venn diagram of sequences retrieved using patterns and HMMs. (b) Venn diagram of sequences retrieved using length-based HMMs and HMMs created using sequences with undefined length.

Mentions: As most of the family-based signatures exhibited good precision, these were queried against UniProt database16 to discover new AMP members. Proteins thus retrieved were categorized as “Class I”, “Class II” and “Class III” based on the definitions provided by UniProt. “Class – I” are AMPs; “Class – II” are uncharacterized proteins and predicted to be antimicrobial by either GO, InterPro or Pfam annotation and “Class – III” are proteins lacking antimicrobial definition or predicted activity. Accordingly, 1076 Class I, 181 Class II and 880 Class III proteins were retrieved (Fig. 1a). As expected, higher number of Class I proteins were retrieved. Class II and III proteins are promising candidates for AMP discovery. Albeit, presently lacking antimicrobial definition, experimental studies may confirm their antimicrobial activity (as can be seen in this study).


Leveraging family-specific signatures for AMP discovery and high-throughput annotation.

Waghu FH, Barai RS, Idicula-Thomas S - Sci Rep (2016)

(a) Venn diagram of sequences retrieved using patterns and HMMs. (b) Venn diagram of sequences retrieved using length-based HMMs and HMMs created using sequences with undefined length.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836297&req=5

f1: (a) Venn diagram of sequences retrieved using patterns and HMMs. (b) Venn diagram of sequences retrieved using length-based HMMs and HMMs created using sequences with undefined length.
Mentions: As most of the family-based signatures exhibited good precision, these were queried against UniProt database16 to discover new AMP members. Proteins thus retrieved were categorized as “Class I”, “Class II” and “Class III” based on the definitions provided by UniProt. “Class – I” are AMPs; “Class – II” are uncharacterized proteins and predicted to be antimicrobial by either GO, InterPro or Pfam annotation and “Class – III” are proteins lacking antimicrobial definition or predicted activity. Accordingly, 1076 Class I, 181 Class II and 880 Class III proteins were retrieved (Fig. 1a). As expected, higher number of Class I proteins were retrieved. Class II and III proteins are promising candidates for AMP discovery. Albeit, presently lacking antimicrobial definition, experimental studies may confirm their antimicrobial activity (as can be seen in this study).

Bottom Line: As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance.The webserver is available online at www.campsign.bicnirrh.res.in.In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Informatics Centre of Indian Council of Medical Research, National Institute for Research in Reproductive Health, Mumbai-400012, India.

ABSTRACT
Antimicrobial peptides (AMPs) are diverse, biologically active, essential components of the innate immune system. As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance. They are widely researched for their therapeutic potential, especially against multi-drug resistant pathogens. AMPs are known to have family-specific sequence composition, which can be mined for their discovery and rational design. Here, we present a detailed family-based study on AMP families. The study involved the use of sequence signatures represented by patterns and hidden Markov models (HMMs) present in experimentally studied AMPs to identify novel AMPs. Along with AMPs, peptides hitherto lacking antimicrobial annotation were also retrieved and wet-lab studies on randomly selected sequences proved their antimicrobial activity against Escherichia coli. CAMPSign, a webserver has been created for researchers to effortlessly exploit the use of AMP family signatures for identification of AMPs. The webserver is available online at www.campsign.bicnirrh.res.in. In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

No MeSH data available.


Related in: MedlinePlus