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Buetti-Dinh, AntoineORCID iD iconorcid.org/0000-0002-6469-0296
Publications (10 of 16) Show all publications
Buetti-Dinh, A., Galli, V., Bellenberg, S., Ilie, O., Herold, M., Christel, S., . . . Dopson, M. (2019). Deep neural networks outperform human expert's capacity in characterizing bioleaching bacterial biofilm composition. Biotechnology Reports, 22, 1-5, Article ID e00321.
Open this publication in new window or tab >>Deep neural networks outperform human expert's capacity in characterizing bioleaching bacterial biofilm composition
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2019 (English)In: Biotechnology Reports, ISSN 0156-1383, E-ISSN 2215-017X, Vol. 22, p. 1-5, article id e00321Article in journal (Refereed) Published
Abstract [en]

Background: Deep neural networks have been successfully applied to diverse fields of computer vision. However, they only outperform human capacities in a few cases. Methods: The ability of deep neural networks versus human experts to classify microscopy images was tested on biofilm colonization patterns formed on sulfide minerals composed of up to three different bioleaching bacterial species attached to chalcopyrite sample particles. Results: A low number of microscopy images per category (<600) was sufficient for highly efficient computational analysis of the biofilm's bacterial composition. The use of deep neural networks reached an accuracy of classification of ∼90% compared to ∼50% for human experts. Conclusions: Deep neural networks outperform human experts’ capacity in characterizing bacterial biofilm composition involved in the degradation of chalcopyrite. This approach provides an alternative to standard, time-consuming biochemical methods. © 2019 The Author

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Acidophiles, Bacterial biofilm, Biomining, Convolutional neural networks, Deep learning, Microscopy imaging, sulfide, Acidithiobacillus caldus, Article, artificial neural network, bacterium, bacterium culture, biofilm, bioleaching, epifluorescence microscopy, high throughput screening, image analysis, Leptospirillum ferriphilum, microbial colonization, microscopy, nonhuman, performance, priority journal, Sulfobacillus thermosulfidooxidans, training
National Category
Microbiology
Research subject
Ecology, Microbiology
Identifiers
urn:nbn:se:lnu:diva-86412 (URN)10.1016/j.btre.2019.e00321 (DOI)2-s2.0-85063054023 (Scopus ID)
Available from: 2019-07-11 Created: 2019-07-11 Last updated: 2019-10-11Bibliographically approved
Buetti-Dinh, A., Jensen, R. & Friedman, R. (2018). A computational study of hedgehog signalling involved in basal cell carcinoma reveals the potential and limitation of combination therapy. BMC Cancer, 18(1), 1-8, Article ID 569.
Open this publication in new window or tab >>A computational study of hedgehog signalling involved in basal cell carcinoma reveals the potential and limitation of combination therapy
2018 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 18, no 1, p. 1-8, article id 569Article in journal (Refereed) Published
Abstract [en]

Background: The smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations. Methods: We investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC. To examine the potential for combination therapy or other treatments, we further performed knowledge-based simulations of SHH signalling, in the presence or absence of SMO and PI3K/Akt inhibitors. Results: The database analysis revealed that of 18 known mutations associated with Vismodegib-resistance, three were identified in the databases. Treatment of individuals carrying such mutations is thus liable to fail a priori. Analysis of the simulations suggested that a combined inhibition of SMO and the PI3K/Akt signalling pathway may provide an effective reduction in tumour proliferation. However, the inhibition dosage of SMO and PI3K/Akt depended on the activity of phosphodiesterases (PDEs). Under high PDEs activities, SMO became the most important control node of the network. By applying PDEs inhibition, the control potential of SMO decreased and P13K appeared as a significant factor in controlling tumour proliferation. Conclusions: Our systems biology approach employs knowledge-based computer simulations to help interpret the large amount of data available in public databases, and provides application-oriented solutions for improved cancer resistance treatments.

Place, publisher, year, edition, pages
BioMed Central, 2018
National Category
Cancer and Oncology Bioinformatics and Systems Biology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-76627 (URN)10.1186/s12885-018-4451-1 (DOI)000432706500002 ()29776351 (PubMedID)2-s2.0-85047067972 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2015/387
Available from: 2018-07-03 Created: 2018-07-03 Last updated: 2019-08-29Bibliographically approved
Bellenberg, S., Buetti-Dinh, A., Galli, V., Ilie, O., Herold, M., Christel, S., . . . Dopson, M. (2018). Automated Microscopic Analysis of Metal Sulfide Colonization by Acidophilic Microorganisms. Applied and Environmental Microbiology, 84(20), Article ID UNSP e01835-18.
Open this publication in new window or tab >>Automated Microscopic Analysis of Metal Sulfide Colonization by Acidophilic Microorganisms
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2018 (English)In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 84, no 20, article id UNSP e01835-18Article in journal (Refereed) Published
Abstract [en]

Industrial biomining processes are currently focused on metal sulfides and their dissolution, which is catalyzed by acidophilic iron(II)- and/or sulfur-oxidizing microorganisms. Cell attachment on metal sulfides is important for this process. Biofilm formation is necessary for seeding and persistence of the active microbial community in industrial biomining heaps and tank reactors, and it enhances metal release. In this study, we used a method for direct quantification of the mineral-attached cell population on pyrite or chalcopyrite particles in bioleaching experiments by coupling high-throughput, automated epifluorescence microscopy imaging of mineral particles with algorithms for image analysis and cell quantification, thus avoiding human bias in cell counting. The method was validated by quantifying cell attachment on pyrite and chalcopyrite surfaces with axenic cultures of Acidithiobacillus caldus, Leptospirillum ferriphilum, and Sulfobacillus thermosulfidooxidans. The method confirmed the high affinity of L. ferriphilum cells to colonize pyrite and chalcopyrite surfaces and indicated that biofilm dispersal occurs in mature pyrite batch cultures of this species. Deep neural networks were also applied to analyze biofilms of different microbial consortia. Recent analysis of the L. ferriphilum genome revealed the presence of a diffusible soluble factor (DSF) family quorum sensing system. The respective signal compounds are known as biofilm dispersal agents. Biofilm dispersal was confirmed to occur in batch cultures of L. ferriphilum and S. thermosulfidooxidans upon the addition of DSF family signal compounds. IMPORTANCE The presented method for the assessment of mineral colonization allows accurate relative comparisons of the microbial colonization of metal sulfide concentrate particles in a time-resolved manner. Quantitative assessment of the mineral colonization development is important for the compilation of improved mathematical models for metal sulfide dissolution. In addition, deep-learning algorithms proved that axenic or mixed cultures of the three species exhibited characteristic biofilm patterns and predicted the biofilm species composition. The method may be extended to the assessment of microbial colonization on other solid particles and may serve in the optimization of bioleaching processes in laboratory scale experiments with industrially relevant metal sulfide concentrates. Furthermore, the method was used to demonstrate that DSF quorum sensing signals directly influence colonization and dissolution of metal sulfides by mineral-oxidizing bacteria, such as L. ferriphilum and S. thermosulfidooxidans.

Place, publisher, year, edition, pages
American society for microbiology, 2018
Keywords
bioleaching, biofilm formation, biofilm dispersal, image analysis, microbe-mineral interaction, quorum sensing, diffusible soluble factor, biofilms, fluorescent image analysis, microbe-mineral interactions
National Category
Microbiology
Research subject
Ecology, Microbiology
Identifiers
urn:nbn:se:lnu:diva-78464 (URN)10.1128/AEM.01835-18 (DOI)000446206900020 ()30076195 (PubMedID)2-s2.0-85054103905 (Scopus ID)
Available from: 2018-10-24 Created: 2018-10-24 Last updated: 2019-08-29Bibliographically approved
Buetti-Dinh, A. & Friedman, R. (2018). Computer simulations of the signalling network in FLT3+-acute myeloid leukaemia: indications for an optimal dosage of inhibitors against FLT3 and CDK6. BMC Bioinformatics, 19, 1-13, Article ID 155.
Open this publication in new window or tab >>Computer simulations of the signalling network in FLT3+-acute myeloid leukaemia: indications for an optimal dosage of inhibitors against FLT3 and CDK6
2018 (English)In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 19, p. 1-13, article id 155Article in journal (Refereed) Published
Abstract [en]

Background

Mutations in the FMS-like tyrosine kinase 3 (FLT3) are associated with uncontrolled cellular functions that contribute to the development of acute myeloid leukaemia (AML). We performed computer simulations of the FLT3-dependent signalling network in order to study the pathways that are involved in AML development and resistance to targeted therapies.

Results

Analysis of the simulations revealed the presence of alternative pathways through phosphoinositide 3 kinase (PI3K) and SH2-containing sequence proteins (SHC), that could overcome inhibition of FLT3. Inhibition of cyclin dependent kinase 6 (CDK6), a related molecular target, was also tested in the simulation but was not found to yield sufficient benefits alone.

Conclusions

The PI3K pathway provided a basis for resistance to treatments. Alternative signalling pathways could not, however, restore cancer growth signals (proliferation and loss of apoptosis) to the same levels as prior to treatment, which may explain why FLT3 resistance mutations are the most common resistance mechanism. Finally, sensitivity analysis suggested the existence of optimal doses of FLT3 and CDK6 inhibitors in terms of efficacy and toxicity.

Place, publisher, year, edition, pages
London: BioMed Central, 2018
National Category
Bioinformatics and Systems Biology Biochemistry and Molecular Biology Cancer and Oncology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-73804 (URN)10.1186/s12859-018-2145-y (DOI)000431025900001 ()29699481 (PubMedID)2-s2.0-85046037732 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2015/387
Available from: 2018-05-04 Created: 2018-05-04 Last updated: 2019-08-29Bibliographically approved
Christel, S., Herold, M., Bellenberg, S., El Hajjami, M., Buetti-Dinh, A., Pivkine, I. V., . . . Dopson, M. (2018). Multi-omics reveal the lifestyle of the acidophilic, mineral-oxidizing model species Leptospirillum ferriphilumT. Applied and Environmental Microbiology, 4(3), Article ID UNSP e02091-17.
Open this publication in new window or tab >>Multi-omics reveal the lifestyle of the acidophilic, mineral-oxidizing model species Leptospirillum ferriphilumT
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2018 (English)In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 4, no 3, article id UNSP e02091-17Article in journal (Refereed) Published
Abstract [en]

Leptospirillum ferriphilum plays a major role in acidic, metal rich environments where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of this model species' type strain is available, limiting the possibilities to investigate the strategies and adaptations Leptospirillum ferriphilumT applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilumT DSM 14647 obtained by PacBio SMRT long read sequencing for use as a high quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as substrate and bioleaching cultures containing chalcopyrite (CuFeS2). Leptospirillum ferriphilumT adaptations to growth on chalcopyrite included a possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, expression and translation of genes responsible for chemotaxis and motility were enhanced.

Place, publisher, year, edition, pages
American society for microbiology, 2018
National Category
Microbiology
Research subject
Ecology, Microbiology; Ecology, Microbiology
Identifiers
urn:nbn:se:lnu:diva-69199 (URN)10.1128/AEM.02091-17 (DOI)000423770000018 ()2-s2.0-85040673185 (Scopus ID)
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2019-08-29Bibliographically approved
Christel, S., Herold, M., Bellenberg, S., Buetti-Dinh, A., El Hajjami, M., Pivkin, I., . . . Dopson, M. (2018). Weak Iron Oxidation by Sulfobacillus thermosulfidooxidans Maintains a Favorable Redox Potential for Chalcopyrite Bioleaching. Frontiers in Microbiology, 9, Article ID 3059.
Open this publication in new window or tab >>Weak Iron Oxidation by Sulfobacillus thermosulfidooxidans Maintains a Favorable Redox Potential for Chalcopyrite Bioleaching
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2018 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 9, article id 3059Article in journal (Refereed) Published
Abstract [en]

Bioleaching is an emerging technology, describing the microbially assisted dissolution of sulfidicores that provides a more environmentally friendly alternative to many traditional metal extractionmethods, such as roasting or smelting. Industrial interest increases steadily and today, circa 15-20%of the world’s copper production can be traced back to this method. However, bioleaching of theworld’s most abundant copper mineral chalcopyrite suffers from low dissolution rates, oftenattributed to passivating layers, which need to be overcome to use this technology to its full potential.To prevent these passivating layers from forming, leaching needs to occur at a lowoxidation/reduction potential (ORP), but chemical redox control in bioleaching heaps is difficult andcostly. As an alternative, selected weak iron-oxidizers could be employed that are incapable ofscavenging exceedingly low concentrations of iron and therefore, raise the ORP just above the onsetof bioleaching, but not high enough to allow for the occurrence of passivation. In this study, wereport that microbial iron oxidation by Sulfobacillus thermosulfidooxidans meets these specifications.Chalcopyrite concentrate bioleaching experiments with S. thermosulfidooxidans as the sole ironoxidizer exhibited significantly lower redox potentials and higher release of copper compared tocommunities containing the strong iron oxidizer Leptospirillum ferriphilum. Transcriptomic responseto single and co-culture of these two iron oxidizers was studied and revealed a greatly decreasednumber of mRNA transcripts ascribed to iron oxidation in S. thermosulfidooxidans when cultured inthe presence of L. ferriphilum. This allowed for the identification of genes potentially responsible forS. thermosulfidooxidans’ weaker iron oxidation to be studied in the future, as well as underlined theneed for mechanisms to control the microbial population in bioleaching heaps

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
redox control, microbial, bioleaching, chalcopyrite, iron oxidation, sulfobacillus, leptospirillum
National Category
Microbiology
Research subject
Ecology, Microbiology
Identifiers
urn:nbn:se:lnu:diva-77662 (URN)10.3389/fmicb.2018.03059 (DOI)000453089800001 ()30631311 (PubMedID)2-s2.0-85058415510 (Scopus ID)
Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2019-08-29Bibliographically approved
Christel, S., Fridlund, J., Buetti-Dinh, A., Buck, M., Watkin, E. L. & Dopson, M. (2016). RNA transcript sequencing reveals inorganic sulfur compound oxidation pathways in the acidophile Acidithiobacillus ferrivorans. FEMS Microbiology Letters, 363(7), Article ID fnw057.
Open this publication in new window or tab >>RNA transcript sequencing reveals inorganic sulfur compound oxidation pathways in the acidophile Acidithiobacillus ferrivorans
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2016 (English)In: FEMS Microbiology Letters, ISSN 0378-1097, E-ISSN 1574-6968, Vol. 363, no 7, article id fnw057Article in journal (Refereed) Published
Abstract [en]

Acidithiobacillus ferrivorans is an acidophile implicated in low-temperature biomining for the recovery of metals from sulfide minerals. Acidithiobacillus ferrivorans obtains its energy from the oxidation of inorganic sulfur compounds, and genes encoding several alternative pathways have been identified. Next-generation sequencing of At. ferrivorans RNA transcripts identified the genes coding for metabolic and electron transport proteins for energy conservation from tetrathionate as electron donor. RNA transcripts suggested that tetrathionate was hydrolyzed by the tetH1 gene product to form thiosulfate, elemental sulfur and sulfate. Despite two of the genes being truncated, RNA transcripts for the SoxXYZAB complex had higher levels than for thiosulfate quinone oxidoreductase (doxDA genes). However, a lack of heme-binding sites in soxX suggested that DoxDA was responsible for thiosulfate metabolism. Higher RNA transcript counts also suggested that elemental sulfur was metabolized by heterodisulfide reductase (hdr genes) rather than sulfur oxygenase reductase (sor). The sulfite produced as a product of heterodisulfide reductase was suggested to be oxidized by a pathway involving the sat gene product or abiotically react with elemental sulfur to form thiosulfate. Finally, several electron transport complexes were involved in energy conservation. This study has elucidated the previously unknown At. ferrivorans tetrathionate metabolic pathway that is important in biomining.

National Category
Microbiology
Research subject
Ecology, Microbiology
Identifiers
urn:nbn:se:lnu:diva-50210 (URN)10.1093/femsle/fnw057 (DOI)000377967800008 ()2-s2.0-84993237658 (Scopus ID)
Available from: 2016-03-04 Created: 2016-03-04 Last updated: 2018-10-24Bibliographically approved
Buetti-Dinh, A., O'Hare, T. & Friedman, R. (2016). Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy. PLoS ONE, 11(9), Article ID e0163011.
Open this publication in new window or tab >>Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0163011Article in journal (Refereed) Published
Abstract [en]

A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival. Our results also highlight the importance of a group of interleukins together with the Janus kinase 3 (JAK3) / signal transducer and activator of transcription 3 (STAT3) signalling in the development of NPM-ALK derived ALCL. Depending on the activity of JAK3 and STAT3, the system may also be sensitive to activation of protein tyrosine phosphatase-1 (SHP1), which has an inhibitory effect on cell survival and proliferation. The identification of signalling pathways active in tumourigenic processes is of fundamental importance for effective therapies. The prediction of alternative pathways that circumvent classical therapeutic targets opens the way to preventive approaches for countering the emergence of cancer resistance.

National Category
Bioinformatics and Systems Biology Cancer and Oncology
Research subject
Chemistry, Biotechnology
Identifiers
urn:nbn:se:lnu:diva-57492 (URN)10.1371/journal.pone.0163011 (DOI)000384167300019 ()2-s2.0-84992025478 (Scopus ID)
Available from: 2016-10-20 Created: 2016-10-20 Last updated: 2018-11-02Bibliographically approved
Buetti-Dinh, A., Dethlefsen, O., Friedman, R. & Dopson, M. (2016). Transcriptomic analysis reveals how a lack of potassium ions increases Sulfolobus acidocaldarius sensitivity to pH changes. Microbiology, 162(8), 1422-1434
Open this publication in new window or tab >>Transcriptomic analysis reveals how a lack of potassium ions increases Sulfolobus acidocaldarius sensitivity to pH changes
2016 (English)In: Microbiology, ISSN 1350-0872, E-ISSN 1465-2080, Vol. 162, no 8, p. 1422-1434Article in journal (Refereed) Published
Abstract [en]

Extremely acidophilic microorganisms (optimum growth pH of ≤3) maintain a near neutral cytoplasmic pH via several homeostatic mechanisms, including an inside positive membrane potential created by potassium ions. Transcriptomic responses to pH stress in the thermoacidophilic archaeon, Sulfolobus acidocaldarius were investigated by growing cells without added sodium and/or potassium ions at both optimal and sub-optimal pH. Culturing the cells in the absence of added sodium or potassium ions resulted in a reduced growth rate compared to full-salt conditions as well as 43 and 75 significantly different RNA transcript ratios, respectively. Differentially expressed RNA transcripts during growth in the absence of added sodium ions included genes coding for permeases, a sodium/proline transporter and electron transport proteins. In contrast, culturing without added potassium ions resulted in higher RNA transcripts for similar genes as a lack of sodium ions plus genes related to spermidine that has a general role in response to stress and a decarboxylase that potentially consumes protons. The greatest RNA transcript response occurred when S. acidocaldarius cells were grown in the absence of potassium and/or sodium at a sub-optimal pH. These adaptations included those listed above plus osmoregulated glucans and mechanosensitive channels that have previously been shown to respond to osmotic stress. In addition, data analyses revealed two co-expressed IclR family transcriptional regulator genes with a previously unknown role in the S. acidocaldarius pH stress response. Our study provides additional evidence towards the importance of potassium in acidophile growth at acidic pH.

National Category
Microbiology Bioinformatics and Systems Biology
Research subject
Ecology, Microbiology
Identifiers
urn:nbn:se:lnu:diva-57490 (URN)10.1099/mic.0.000314 (DOI)000385271900015 ()27230583 (PubMedID)2-s2.0-84986879631 (Scopus ID)
Available from: 2016-10-20 Created: 2016-10-20 Last updated: 2018-11-02Bibliographically approved
Buetti-Dinh, A. (2015). S100A4 and its role in metastasis – computational integration of data on biological networks.
Open this publication in new window or tab >>S100A4 and its role in metastasis – computational integration of data on biological networks
2015 (English)Other (Other academic)
Series
Global Medical Discovery, ISSN 1929-8536
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-46750 (URN)
Available from: 2015-10-13 Created: 2015-10-13 Last updated: 2016-10-12Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6469-0296

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