Fluctuation AnaLysis CalculatOR: a web tool for the determination of mutation rate using Luria–Delbrück fluctuation analysis
Open accessAbstract
The FALCOR rate calculator is a web tool designed for use with Luria–Delbrück fluctuation analysis to calculate the frequency and rate from various mutation assays in bacteria and yeast. Three calculation methods are available: MSS-MLE, Lea-Coulson median, and frequency.
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Claims the paper makes
1 of 10 cited sources checked · 1 supported · 0 flagged
- Premisecitation
Frequency is not a sufficiently accurate measure of mutation.
“As such, frequency is not a sufficiently accurate measure of mutation; mutation rate (m/N t ) should always be calculated (Rosche and Foster, 2000).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Rosche and Foster, 2000 source
- Premisereasoning
The frequency (r/Nt) varies greatly even if the number of mutational events, m, is the same.
“These factors cause the frequency (r/N t ) to vary greatly, even if the number of mutational events, m, is the same.”
Quote in the paperSubstantial claim - Premisecitation
The Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) is the best method available to date.
“The Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) is the best method available to date (Zheng, 2002); it is the most accurate and, unlike the LC method, is valid over all values of r and m.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zheng, 2002 source
- Premisecitation
MSS-MLE is the most accurate method.
“The Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) is the best method available to date (Zheng, 2002); it is the most accurate and, unlike the LC method, is valid over all values of r and m.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zheng, 2002 source
- Premisecitation
MSS-MLE is valid over all values of r and m, unlike the LC method.
“The Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) is the best method available to date (Zheng, 2002); it is the most accurate and, unlike the LC method, is valid over all values of r and m.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zheng, 2002 source
- Premisecitation
The natural log of m is normally distributed.
“The confidence intervals are calculated according to the method of Stewart (1994) who discovered that the natural log of m is normally distributed.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Stewart (1994) source
- Classified as probably not a substantial claim. 6
- May combine two claims. 3
Classified as probably not a substantial claim.
Findingnone givenThree calculation methods are available through FALCOR: MSS-MLE, LC, and frequency.
“Three calculation methods are available through this program: (i) Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) method, (ii) Lea-Coulson method of the median (LC) and (iii) frequency.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Findingnone givenFALCOR is a web tool designed for use with Luria-Delbrück fluctuation analysis to calculate the frequency and rate from various mutation assays in bacteria and yeast.
“The program Fluctuation AnaLysis CalculatOR (FALCOR) is a web tool designed for use with Luria-Delbrück fluctuation analysis to calculate the frequency and rate from various mutation assays in bacteria and yeast.”
Quote in the paperSubstantial claim- Rests on an assumption: Accurately determining the rate of genetic events is fundamental to understanding the genes and pathways involved in various cellular processes.
- Rests on an assumption: The complex calculations required place the more accurate methods beyond easy reach of bench scientists.
- Rests on an assumption: The three methods implemented (MSS-MLE, LC, frequency) are the most popular methods for estimating mutation rates.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe Lea-Coulson method of the median (LC) is the classic model for the estimation of mutation rates.
“While the Lea-Coulson method of the median (LC), introduced in 1949 (Lea and Coulson, 1949), is the classic model for the estimation of mutation rates, statistical analyses have evolved to more accurately estimate m.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lea and Coulson, 1949 source
Classified as probably not a substantial claim.
Premisenone givenFluctuation analysis has become the standard method in the field for calculating mutation rates.
“Originally described by Luria and Delbrück (1943), fluctuation analysis has become the standard method in the field for calculating mutation rates.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Luria and Delbrück (1943) source
May combine two claims.
PremisereasoningThe MSS-MLE method calculates the mutation rate from the entire dataset (not just the median), providing more statistical power.
“Furthermore, the MSS-MLE method calculates the mutation rate from the entire dataset (not just the median), providing more statistical power.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Premisenone givenFrequencies are useful for determining the level of induced mutations, where cells are treated before the level of mutation is measured.
“However, frequencies are useful for determining the level of induced mutations, where cells are treated (e.g. with a DNA damaging agent) before the level of mutation is measured.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based). May combine two claims.
Interpretationnone givenFluctuation analysis is easily implemented and can yield highly accurate results when the data are analyzed correctly.
“Fluctuation analysis is easily implemented and can yield highly accurate results when the data are analyzed correctly.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationOther programs for estimating mutation rates require the user to implement source code into other software, whereas FALCOR is readily accessible through Java-enabled web browsers.
“While other programs exist for estimating mutation rates (Lang and Murray, 2008;Zheng, 2002Zheng, , 2005Zheng, , 2007)), these require the user to implement source code into other software (i.e.Wolfram's Mathematica or The MathWorks' Matlab), whereas FALCOR is readily accessible through Java-enabled web browsers.”
Quote in the paperSubstantial claim0 of 3 sources checked
The paper relies on this without support.
Accurately determining the rate of genetic events is fundamental to understanding the genes and pathways involved in various cellular processes.
“Being able to accurately determine the rate of these genetic events is fundamental to understanding the genes and pathways involved in various cellular processes.”
The paper relies on this without support.
The complex calculations required place the more accurate methods beyond easy reach of bench scientists.
“However, the complex calculations required place these more accurate methods beyond easy reach of bench scientists.”
The paper relies on this without support.
The three methods implemented (MSS-MLE, LC, frequency) are the most popular methods for estimating mutation rates.
“To facilitate the use of these complicated methods by bench scientists, we developed a web interface to implement the three most popular methods.”
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“Mutation rates were calculated and corrected for sampling error using the MSS-maximumlikelihood estimator method from the FALCOR fluctuation analysis calculator (http://www.mitochondria.org/protocols/ FALCOR.html) (Hall et al. 2009).”
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“Mutation rate, as indicated, is displayed per 107 mutations/generation (Hall et al. 2009).”
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Low mutational load and high mutation rate variation in gut commensal bacteria
Ramiro, R. S., Durão, P., Bank, C., & Gordo, I. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000617 · Cited by 68 · see citing works
Remigi, P., Capela, D., Clérissi, C., Tasse, L., Torchet, R., Bouchez, O., Batut, J., Cruveiller, S., Rocha, E. P. C., & Masson‐Boivin, C. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001942 · Cited by 77 · see citing works
“Mutation rates were calculated using the Ma-Sandri-Sarkar maximum likelihood (MSS-ML) method [27], as implemented by the Falcor web tool [58].”
Anaerobically Grown Escherichia coli Has an Enhanced Mutation Rate and Distinct Mutational Spectra
Shewaramani, S., Finn, T. J., Leahy, S. C., Kassen, R., Rainey, P. B., & Moon, C. D. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006570 · Cited by 65 · see citing works
Ma, Z., Kim, D. H., Adesogan, A. T., et al. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b00894 · Cited by 74 · see citing works
A TetR-like regulator broadly affects the expressions of diverse genes in Mycobacterium smegmatis
Yang, M., Gao, C., Cui, T., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr830 · Cited by 72 · see citing works
<i>bz-rates</i>: A Web Tool to Estimate Mutation Rates from Fluctuation Analysis
Gillet-Markowska, A., Louvel, G., & Fischer, G. (2015) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.115.019836 · Cited by 58 · see citing works
“In the case of differential growth rate, several estimators that jointly calculate m and b have long been made available (Koch 1982; Jones 1994; Jaeger and Sarkar 1995; Zheng 2002, 2005; Hamon and Ycart 2012).”
BackgroundMethodResultInfluentialLong, H., Sung, W., Miller, S. F., Ackerman, M. S., Doak, T. G., & Lynch, M. (2014) · Genome Biology and Evolution · doi:10.1093/gbe/evu284 · Cited by 60 · see citing works
“Fluctuation AnaLysis CalculatOR (FALCOR): a web tool for the determination of mutation rate using Luria-Delbruck fluctuation analysis.”
MethodEngineered bacterial orthogonal DNA replication system for continuous evolution
Tian, R., Zhao, R., Guo, H., Yan, K., Wang, C., Lu, C., Lv, X., Li, J., Liu, L., Du, G., et al. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01387-2 · Cited by 72 · see citing works
Radchenko, E. A., McGinty, R. J., Aksenova, A. Y., Neil, A. J., & Mirkin, S. M. (2018) · Methods in Molecular Biology · doi:10.1007/978-1-4939-7306-4_29 · Cited by 57 · see citing works
Background Mutational Features of the Radiation-Resistant Bacterium Deinococcus radiodurans
Long, H., Küçükyıldırım, S., Sung, W., Williams, E., Lee, H., Ackerman, M. S., Doak, T. G., Tang, H., & Lynch, M. (2015) · Molecular Biology and Evolution · doi:10.1093/molbev/msv119 · Cited by 63 · see citing works
“The mutation rate and 95% confidence interval were then calculated using the Ma–Sandri–Sarkar Maximum-Likelihood Estimator method in FALCOR (Hall et al. 2009).”
MethodEffective polyploidy causes phenotypic delay and influences bacterial evolvability
Sun, L., Alexander, H. K., Bogos, B., Kiviet, D. J., Ackermann, M., & Bonhoeffer, S. (2018) · PLOS Biology · doi:10.1371/journal.pbio.2004644 · Cited by 53 · see citing works
Piazza, A., Serero, A., Boulé, J.-B., Legoix-Né, P., Lopes, J., & Nicolas, A. G. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003033 · Cited by 68 · see citing works
“The GCR rate ( M ) as well as the upper and lower 95% confidence intervals ( 95% CI ) have been calculated from r and N t with Falcor [ 69 ] using the Lea and Coulson method of the median .”
MethodUmenhoffer, K., Draskovits, G., Nyerges, Á., Karcagi, I., Bogos, B., Tímár, E., Csörgő, B., Herczeg, R., Nagy, I., Fehér, T., et al. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00378 · Cited by 58 · see citing works
Characterization of Chromosome Stability in Diploid, Polyploid and Hybrid Yeast Cells
Kumaran, R., Yang, S.-Y., & Leu, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068094 · Cited by 62 · see citing works
Torres‐Barceló, C., Kojadinovic, M., Moxon, R. E., et al. (2015) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2015.0885 · Cited by 67 · see citing works
Wambaugh, M. A., Shakya, V. P. S., Lewis, A. J., Mulvey, M. A., & Brown, J. C. S. (2017) · PLOS Biology · doi:10.1371/journal.pbio.2001644 · Cited by 63 · see citing works
Oxidative stress drives mutagenesis through transcription-coupled repair in bacteria
Carvajal-Garcia, J., Samadpour, A. N., Viera, A. J. H., & Merrikh, H. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2300761120 · Cited by 63 · see citing works
Hiramatsu, K., Igarashi, M., Morimoto, Y., Baba, T., Umekita, M., & Akamatsu, Y. (2012) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2012.02.007 · Cited by 62 · see citing works
Sousa, A., Ramiro, R. S., Barroso-Batista, J., Güleresi, D., Lourenço, M., & Gordo, I. (2017) · Molecular Biology and Evolution · doi:10.1093/molbev/msx221 · Cited by 52 · see citing works
“The number of spontaneous gat-positive mutants and total number of cells grown on LB were used to estimate the mutation rate using the maximum likelihood approach as implemented in FALCOR (Hall et al. 2009).”
MethodHuang, H., Chen, S., Pan, L., et al. (2014) · Oncology Reports · doi:10.3892/or.2014.3584 · Cited by 61 · see citing works
FANCD2 binding identifies conserved fragile sites at large transcribed genes in avian cells
Pentzold, C., Shah, S. A., Hansen, N. R., Tallec, B. L., Seguin‐Orlando, A., Debatisse, M., Lisby, M., & Oestergaard, V. H. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1260 · Cited by 55 · see citing works
Evidence of a Mild Mutator Phenotype in Cambodian Plasmodium falciparum Malaria Parasites
Lee, A. H., & Fidock, D. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154166 · Cited by 60 · see citing works
Conditional DNA repair mutants enable highly precise genome engineering
Nyerges, Á., Csörgő, B., Nagy, I., Latinovics, D., Szamecz, B., Pósfai, G., & Pál, C. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku105 · Cited by 52 · see citing works
Founder niche constrains evolutionary adaptive radiation
Flohr, R. C. E., Blom, C. J., Rainey, P. B., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310310110 · Cited by 59 · see citing works
Kaushal, S., Wollmuth, C. E., Das, K., Hile, S., Regan, S. B., Barnes, R. P., Haouzi, A., Lee, S.-M., House, N., Guyumdzhyan, M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.103 · Cited by 50 · see citing works
“A rate of FOAR Ade+ was calculated using the method of the median using the FALCOR online calculator (Hall et al., 2009).”
Suárez, G. A., Renda, B. A., Dasgupta, A., et al. (2017) · Applied and Environmental Microbiology · doi:10.1128/aem.01025-17 · Cited by 44 · see citing works
Torres‐Barceló, C., Cabot, G., Oliver, A., et al. (2013) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2013.0007 · Cited by 57 · see citing works
The mutational landscape of quinolone resistance in Escherichia coli
Bhatnagar, K., & Wong, A. (2019) · PLoS ONE · doi:10.1371/journal.pone.0224650 · Cited by 50 · see citing works
Nagel, M., Reuter, T., Jansen, A., Szekat, C., & Bierbaum, G. (2010) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2010.08.021 · Cited by 51 · see citing works
Bochman, M. L., Paeschke, K., Chan, A., & Zakian, V. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2013.12.037 · Cited by 47 · see citing works
“GCR rates (per 10 9 mutations/generation) and 95% confidence intervals were calculated using the FALCOR web server and MMS Maximum Likelihood Method (Hall et al., 2009).”
MethodMeasuring Mutation Rates Using the Luria-Delbrück Fluctuation Assay
Lang, G. I. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7306-4_3 · Cited by 46 · see citing works
“Alternatively, several web-based tools exist for analyzing fluctuation assays [8, 9].”
BackgroundKadyrova, L. Y., Mertz, T. M., Zhang, Y., Northam, M. R., Sheng, Z., Lobachev, K. S., Shcherbakova, P. V., & Kadyrov, F. A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003899 · Cited by 51 · see citing works
Dalia, T. N., Yoon, S. H., Galli, E., Barre, F., Waters, C. M., & Dalia, A. B. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx496 · Cited by 44 · see citing works
Lourenço, M., Ramiro, R. S., Güleresi, D., Barroso-Batista, J., Xavier, K. B., Gordo, I., & Sousa, A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006420 · Cited by 43 · see citing works
The sliding clamp tethers the endonuclease domain of MutL to DNA
Pillon, M. C., Babu, V. M. P., Randall, J. R., Cai, J., Simmons, L. A., Sutton, M. D., & Guarné, A. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv918 · Cited by 48 · see citing works
“Mutation rates were calculated using FALCOR, a Ma-Sandri-Sarkar Maximum Likelihood Estimator (37).”
MutS2 Promotes Homologous Recombination in Bacillus subtilis
Burby, P. E., & Simmons, L. A. (2016) · Journal of Bacteriology · doi:10.1128/jb.00682-16 · Cited by 46 · see citing works
Sublethal streptomycin concentrations and lytic bacteriophage together promote resistance evolution
Cairns, J., Becks, L., Jalasvuori, M., & Hiltunen, T. (2016) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0040 · Cited by 46 · see citing works
Glutathione is essential to preserve nuclear function and cell survival under oxidative stress
Hatem, E., Berthonaud, V., Dardalhon, M., Lagniel, G., Baudouin‐Cornu, P., Huang, M., Labarre, J., & Chdin, S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.10.746 · Cited by 49 · see citing works
Glutathione is essential to preserve nuclear function and cell survival under oxidative stress
Hatem, E., Berthonaud, V., Dardalhon, M., Lagniel, G., Baudouin‐Cornu, P., Huang, M., Labarre, J., & Chédin, S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.807 · Cited by 48 · see citing works
Emergence of DNA Polymerase ε Antimutators That Escape Error-Induced Extinction in Yeast
Williams, L. N., Herr, A. J., & Preston, B. D. (2013) · Genetics · doi:10.1534/genetics.112.146910 · Cited by 46 · see citing works
“The FALCOR program uses these values to calculate a maximum-likelihood estimate of mutation rate expressed per cell division (see Hall et al. 2009 and references therein).”
MethodInfluentialWang, Y., Huang, Y., Xue, C., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.241802 · Cited by 49 · see citing works
Stimulation of Chromosomal Rearrangements by Ribonucleotides
Sedam, H. N. C., Lujan, S. A., Chapman, M. J., Cornélio, D. A., Sharif, R., Williams, J. S., Clark, A., Camilo, F., Kunkel, T. A., & Argueso, J. L. (2015) · Genetics · doi:10.1534/genetics.115.181149 · Cited by 47 · see citing works
- Authors
- Hall, B. M., Ma, C.-X., Liang, P., & Singh, K. K.
- Affiliations
- Roswell Park Comprehensive Cancer Center (US)
- Corresponding author
- Hall, Brandon M.
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-04-15
- Volume
- 25
- Issue
- 12
- Pages
- 1564-1565
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC2687991
- OpenAlex
- W2107861779
- Cited by
- 375
- References
- 13
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 19 · 2023: 20 · 2022: 14 · 2021: 8 · 2020: 13 · 2019: 27 · 2018: 35 · 2017: 46 · 2016: 38 · 2015: 28 · 2014: 29 · 2013: 26 · 2012: 21
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bioinformatics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (121904, R01‐grant, 113655)
- U.S. Public Health Service (R01 113655, R01 121904)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- mutation rate estimation, web-based calculator, mutation frequency, Java applets
- MeSH terms
- Mutation, Software, Likelihood Functions, Computational Biology, Internet, Databases, Genetic
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