PredictionofIonizingRadiationResistanceinBacteria
UsingaMultipleInstanceLearningModel
Zoghlami M., Aridhi S., Sghaier H., Maddouri M., Mephu Nguifo E.
In Journal of Computational Biology 2016 23(1):10-20
Oral presentation at JOBIM 2016
PFAuBI Journée,March30,2017,Clermont-Ferrand
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Ionizing-Radiation Resistant Bacteria (IRRB)
are used for the bioremediation of nuclear wastes.
Deinococus Radiodurans
Ø detoxify pollutants in sites containing mixed metal, organic, and
radioactive toxic wastes.
in vitro and in silico works studied the causes of the high resistance of these
organisms to ionizing radiation
Ø determine peculiar features in their genomes and
Ø improve the treatment of radioactive wastes.
PFAuBIJournée– March30,2017
2 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Radioresistant bacterium ?
PFAuBIJournée– March30,2017
Radiosensitive bacterium ?
3 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Radioresistant bacteria & applications
Gabani, P. and Singh, O.V. (2013) Radiation-resistant extremophiles and
their potential in biotechnology and therapeutics, Appl Microbiol Biotechnol,
97, 993–1004.
Singh, O.V. and Gabani, P. (2011) Extremophiles: radiation resistance microbial
reserves and therapeutic implications, Journal of applied microbiology, 110, 851–861.
Brim,H.,etal.(2003)EngineeringDeinococcus geothermalis forbioremediation of
high-temperature radioactivewaste environments,Appl EnvironMicrobiol,69,4575–
4582.
Brim,H.,etal.(2000)EngineeringDeinococcus radiodurans formetal remediation in
radioactivemixedwaste environments,NatBiotechnol,18,85–90.
PFAuBIJournée– March30,2017
4 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Application of radioresistant bacteria in
environmental biotechnology
Problem: Elevated concentrations of uranium and other
radionuclides are present in mining and milling areas, at sites
where uranium ore was processed, and where uranium was
enriched. Regulatory bodies may require this uncontrolled source
of radiation to be remediated to acceptable levels.
Solution: Radioresistant bacteria can be applied to bioremediate
metal and radionuclide contamination.
Newsome,L.,Morris,K.andLloyd,J.R.(2014)Thebiogeochemistryandbioremediationofuraniumand
otherpriorityradionuclides,ChemicalGeology,363,164–184.
PFAuBIJournée– March30,2017
5 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Radioresistance has been observed in a broad range of microorganisms of the domain
Bacteria
A 16S-rRNA-genesequence-based
phylogeny of the
main lineages
of the domain
Bacteria.
Thebranchesinred arethose inwhich ionizing-radiation-resistant taxahavebeen
described.Thescale barrepresents 10inferred nucleotide substitutionsper100
nucleotides.
Cox MM, Battista JR. Deinococcus radiodurans - the consummate
survivor. Nat Rev Microbiol. 2005; 3(11):882-892.
PFAuBIJournée– March30,2017
6 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Can phylogenetic relationships alone be
used to predict the phenotype of
radioresistance? NO.
Example:
Thermus thermophilus
(radiosensitive)and
Deinococcus radiodurans
(radioresistant)belongtoa
distinctbacterialphylogenetic
cladebuthaveremarkably
differentphenotypes.
Omelchenko,M.V.,etal.(2005)Comparativegenomics ofThermus
thermophilus andDeinococcus radiodurans:divergentroutesof
adaptationtothermophily andradiationresistance, BMCEvol Biol,
5,57.
PFAuBIJournée– March30,2017
7 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
[Daly et al., Science 2004]:
§ IRRB accumulates about 300 times more manganese ions (Mn(II)) than
IRSB
[Sghaier et al., BMC Genomics 2009]:
§ All basal DNA repair genes in IRRB, unlike many of their orthologs in
IRSB, are subject to positive selection.
Challenge
in silico prediction of ionizing radiation resistance in bacteria
- using only amino-acid sequences
PFAuBIJournée– March30,2017
8 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
DB = {X1, …, Xn}: a bacteria database
Xi = {pi1, …, pik}: a bag of proteins
yi = {IRRB; IRSB}: a class label
Phenotypic prediction of IRRB: Multiple instance learning (MIL)
Given a query bacterium Q = {p1, …, pk}, the classifier uses primary structure
of basal DNA repair proteins in Q and in each bag of DB to predict the label of Q.
PFAuBIJournée– March30,2017
9 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Algorithms:
Ø Diverse Density [Maron et al., 1998]
Ø Citation-kNN and Bayesian-kNN [Wang et al., 2000]
Application to drug activity prediction [Fu et al., 2012]
Existing works
Ø Use an attribute-value format to represent their data.
Ø Need a unique set of attributes for each instance description
Ø Not suitable for phenotypic prediction of IRRB.
A novel approach is needed !
PFAuBIJournée– March30,2017
10 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Learning database
PX11
P X 12
PX21
S12
B2
PX2k
å
R1
å
R2
å
IRRB or
IRSB
Sk2
...
...
...
PXn1
PXn2
S22
...
...
Pqk
S21
Sk1
...
Pq2
B1
P X 1k
PX22
Aggregation
S11
...
...
Pq1
Similarity measurement
Query Q
Similarity scores
S1k
PXnk
PFAuBIJournée– March30,2017
S2k
...
...
Bn
å
Rk
Skk
11 /23
Context and motivations
Multiple Instance Problem
Proposed Approach
Experiments
Conclusion and prospects
Conclusion
Predicting ionizing-radiation-resistance remains challenging
Formalization as a multiple instance problem
Description of a novel approach: MIL-ALIGN
First results of MIL-ALIGN are satisfactory
MIL-ALIGN is available online at http://www.isima.fr/~mephu/MIL/
PFAuBIJournée– March30,2017
12 /23
Acknowledgments
• Support of the French-Tunisian project: CNRS / DGRST
[IRRB 11/R 14-09].
PFAuBIJournée– March30,2017
13 /23