Quantitative Toxicogenomics assay Lengths, Functional G ... · Membrane, cell wall and cell...

Electronic Supplementary Information for

Toxicity of Single-Walled Carbon Nanotubes (SWCNTs): Effect of

Lengths, Functional Groups and Electronic Structures Revealed by a

Quantitative Toxicogenomics assay

Tao Jiang1, Carlo Alberto Amadei2, Na Gou1,4, Yishan Lin1,4, Jiaqi Lan 1,3*, Chad D.

Vecitis3, April Z. Gu4*

1. Department of Civil and Environmental Engineering, Northeastern University, 360

Huntington Ave, Boston, MA 02115

2. John A. Paulson School of Engineering and Applied Sciences, Harvard University,

Cambridge, MA 02138

3. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union

Medical College, Beijing, 100050, China

4. School of Civil and Environmental Engineering, Cornell University, 220 Hollister Dr.,

Ithaca, NY 14853

* Corresponding authors: [email protected], [email protected]

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Electronic Supplementary Material (ESI) for Environmental Science: Nano.This journal is © The Royal Society of Chemistry 2020

Table S1. Selected GFP-fused reporter yeast library of an assembly of proteins involved in different known cellular stress response pathways.

Stress Function Pathway Protein involvedTrehalose synthesis TPS1, TPS2 Metabolism Osmotic stress HOG1 Signal transduction TPK1, TPK2, CDC28

General stress response General

function Apoptosis CDC48, NMA111, Tat-D, FIS1

Sensor/regulatorYap1p regulationSkn7p regulation Msn2p regulation

YAP1, YBP1SKN7, SLN1MSN2

Glutathione/ Glutaredoxin

GlutathioneGlutaredoxin

GSH1, GSH2GRX1, GRX2

Thioredoxin Thioredoxin TRX1, TRX2, TRX3

Oxidative stress

Defense systemEnzymatic system

SODCatalaseCYC related

SOD1, SOD2, CCS1CTT1CCP1

Membrane, cell wall and cell structure PUN1, HSP12ATP-binding cassette (ABC) transporters PDR1, PDR3, YCF1,

PDR5, SNQ2, BPT1, ATM1Chemical

stress Major facilitator superfamily (MFS) transporters

FLR1, QDR2, ATR1, TPO1, AQR1, QDR3, TOP2

Molecular chaperones HSP104, HSP42, HSP78, HSP26

Cytosolic unfolded protein response (cytUPR)

Ubiquitin-proteasome system

UBC5, UBC8

Sensor/regulator IRE1, HAC1Molecular chaperones KAR2Endoplasmic

reticulum UPR (erUPR) ER-associated protein

degradation (ERAD)UBC1, UBC7

Molecular chaperones HSP60, HSP78Mitochondrial UPR (mtUPR) Proteolytic system OXA1, PIM1

Protein stress

Autophagy ATG1, UTH1DNA damage signaling (DDS)

CHK1, RAD9

Direct reversal repair (DRR)

PHR1

Translesion synthesis (TLS) RAD30Base excision repair (BER) OGG1, NTG1, NTG2,

UNG1, MAG1

DNA stress DNA repair

Nucleotide excision repair (NER)

RAD4

2

Mismatch repair (MMR) MSH2Double strand break (DSB) XRS2, MRE11Homologous recombination (HR)

RAD51

Non-homologous end joining (NHEJ)

YKU70

Toxicogenomics Assay Data Processing

Details of data processing for the yeast toxicogenomics assay were described in our

previous studies 1-3. Briefly, OD and GFP raw data from the measurements were firstly

corrected for any interference due to the media by subtracting the OD and GFP of the well

with the blank control. The corrected OD and GFP signals are referred to as ODcorrected and

GFPcorrected, respectively. The corrected GFP signal (GFPcorrected) was then normalized to

the cell numbers in the well (ODcorrected) as P = GFPcorrected/ODcorrected. The P values was

then corrected for the vehicle internal control (housekeeping gene PGK1 with medium

control on each plate) to normalize different plates among the replicates, which is denoted

as Q. The altered expression level of a given protein at each time point because of

nanomaterial exposure (termed as induction factor, I) is defined as I = Qexperiment/Qcontrol;

where Qexperiment is the internal control (PGK1) normalized P in experimental conditions

with chemical exposure, and Qcontrol is the internal control normalized P in the vehicle

control conditions without any nanomaterial exposure. The induction factor, I < 1 indicates

downregulation and the I > 1 indicates the upregulation of the biomarkers due to the

chemical exposure. The Protein Expression Level Index, PELI, was calculated to aggregate

the time series altered expression into a quantitative toxicity index. The chemical induced

PELI of the protein was calculated as,

3

[1]𝑃𝐸𝐿𝐼𝑂𝑅𝐹,𝑖 =

𝑡

∫𝑡 = 0

𝐼𝑑𝑡

𝑇;𝑤ℎ𝑒𝑟𝑒 𝐼 = 1, 𝑖𝑓 𝐼 ≤ 1, 𝑒𝑙𝑠𝑒 𝐼 = 𝐼.

Where, t is the exposure time in every time-step and T is the total exposure time.

The pathway activation responses were obtained by integrating the expression

changes of all tested protein markers (ORFs) in a pathway as,

[2]𝑃𝐸𝐿𝐼𝑝𝑎𝑡ℎ𝑤𝑎𝑦,𝑗 =

𝑛

∑𝑖 = 1

𝑤𝑖 × 𝑃𝐸𝐿𝐼𝑂𝑅𝐹,𝑖

𝑛

Where, n is the number of ORFs in a particular pathway, and wi is the weight factor of

ORFs. The value of 1 was assigned for all wi in this study.

References:

1. Lan, J., Gou, N., Gao, C., He, M., & Gu, A. Z. (2014). Comparative and mechanistic

genotoxicity assessment of nanomaterials via a quantitative toxicogenomics approach

across multiple species. Environmental Science & Technology, 48 (21), 12937-12945.

2. Lan, J., Hu, M., Gao, C., Alshawabkeh, A., & Gu, A. Z. (2015). Toxicity assessment of

4-methyl-1-cyclohexanemethanol and its metabolites in response to a recent chemical spill

in west virginia, USA. Environmental Science & Technology, 49 (10), 6284-6293.

3. Lan, J., Gou, N., Rahman, S. M., Gao, C., He, M., & Gu, A. Z. (2016). A quantitative

toxicogenomics assay for high-throughput and mechanistic genotoxicity assessment and

screening of environmental pollutants. Environmental Science & Technology, 50 (6),

3202-3214.

Characterization and Purity of Nanomaterials

4

The Nanointegris metallic and semiconducting are characterized by the

manufacturer in detail and raw data (UV-vis for chirality and diameter, AFM for length,

NAA for metal impurity, TGA for all impurities, Raman for amorphous carbon and defects)

can be found in their technical datasheet (http://nanointegris.com/our-products/metallic-

swnts-isonanotubes-m/). The metallic and semiconducting SWCNT were further purified

by first heating to 300 oC in an oven for 4 h to remove amorphous carbon (Vecitis et al.,

ACS Nano, 2010). The SWCNT were then dispersed by bath sonication in concentrated

HCl and heated to 60 oC overnight to remove any residual metals. The SWCNT are

expensive (~$1000 USD per mg) thus there was not enough sample for destructive

techniques such as XPS or TGA. TEM images indicated there were no observable metal

impurities and image analysis yielded an average diameter of ~1.4 nm. Raman

spectroscopy gave a G/D peak ratio of > 2 indicating minimal amorphous carbon impurities

and RBM peak analysis again yielded an average diameter of ~1.4 nm. For the long/short/-

COOH/-OH SWCNT, the sample quantity was sufficient for XPS elemental analysis. The

XPS detection limit was 0.1%, thus a non-detect indicates that an element is < 0.1% in the

sample.

5

SWCNT Long Short -COOH -OHIC5 (mg/mL) 0.8829 0.8759 0.8539 0.8314p-value 0.0075 0.0211 0.0052 0.0240

Figure S1. Cytotoxicity of plain and functionalized SWCNTs in human A549 cells for 24 h exposure. The curves were generated by Four Parameter Logistic (4PL) nonlinear regression model. Significant cytotoxicity was defined as survival percentage < 95% (IC5 indicated by the dashed line). The IC5 was calculated as the concentration with survival percentage = 95%. Mean ± SD, n = 3.

6

Figure S2. Protein expression profiles on the basis of PELI values of the 74 stress biomarkers in yeast in response to the 6 studied single-walled carbon nanotubes (SWCNTs). X-axis bottom: sample names and concentrations of the SWCNTs. C1-C6 indicate concentrations 1-6, which are 0.031, 0.125, 0.5, 2, 8 and 32 mg/L, respectively, for unmodified and functionalized SWCNTs, and 0.0078, 0.031, 0.125, 0.5, 2 and 8 mg/L for metallic and semiconducting SWCNTs. Y-axis left: list of proteins categorized within five stress categories (captions shown at bottom). Y-axis right: scale of PELI values. The PELI values beyond 4 were indicated as 4. All tests were performed in triplicate (n = 3).

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Chemical stressGeneral stressDNA damageOxidative stressProtein damageTotal stress

C - SWCNT-COOH

E - Metallic SWCNTChemical stressGeneral stressDNA damageOxidative stressProtein damageTotal stress


A - Long SWCNT


F - SemiconductingSWCNT


D - SWCNT-OH


B - Short SWCNT

Figure S3. Concentration-response curves on the basis of PELI values of the 5 stress categories and total PELI for the 6 studied SWCNTs: (A) long SWCNT, (B) short SWCNT, (C) carboxylated SWCNT, (D) hydroxylated SWCNT, (E) metallic SWCNT, (F) semiconducting SWCNT. The curves were generated by Four Parameter Logistic (4PL) nonlinear regression model. Data points with error bars indicate the PELI values measured at each concentration. Toxicity positive was defined as possessing a PELI value larger than 1.5. X-axis: concentrations of examined SWCNTs (mg/L). Y-axis: PELI. Mean ± SD, n = 3.

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Table S2. Summary of GSEA results for the 6 studied SWCNTs based on toxicogenomics assay in yeast cells

Stress category Protein set size

Enrichment score (ES)

Normalized enrichment score (NES)

Normal p-value

FDR-q value a

Long SWCNT at 0.031 mg/LGeneral 9 -0.41 -1.17 0.28 1.00DNA 17 -0.33 -1.15 0.30 0.60Chemical 15 -0.20 -0.68 0.84 1.00Oxidative 16 -0.20 -0.68 0.83 0.84

Long SWCNT at 0.125 mg/LDNA 17 -0.51 -1.61 0.03 0.11Chemical 15 -0.32 -1.00 0.47 0.70General 9 -0.32 -0.84 0.63 0.65

Long SWCNT at 0.5 mg/LGeneral 9 -0.41 -1.20 0.24 0.99DNA 17 -0.33 -1.17 0.28 0.56Oxidative 16 -0.31 -1.06 0.40 0.52Chemical 15 -0.17 -0.58 0.93 0.92

Long SWCNT at 2 mg/LDNA 17 -0.53 -1.69 0.02 0.06Chemical 15 -0.41 -1.25 0.23 0.33Oxidative 16 -0.32 -1.00 0.46 0.47

Long SWCNT at 8 mg/LDNA 17 -0.60 -1.94 0.00 0.00General 9 -0.31 -0.85 0.66 1.00Oxidative 16 -0.21 -0.66 0.85 1.00Chemical 15 -0.15 -0.49 0.98 0.98

Long SWCNT at 32 mg/LDNA 17 -0.58 -1.62 0.01 0.02Oxidative 16 -0.45 -1.23 0.21 0.20

Short SWCNT at 0.031 mg/LChemical 15 -0.41 -1.36 0.14 0.55General 9 -0.44 -1.26 0.23 0.43Oxidative 16 -0.31 -1.03 0.43 0.57DNA 17 -0.28 -0.94 0.54 0.53

Short SWCNT at 0.125 mg/LDNA 17 -0.40 -1.21 0.27 1.00Chemical 15 -0.29 -0.87 0.65 1.00Oxidative 16 -0.28 -0.85 0.66 1.00General 9 -0.30 -0.79 0.72 0.91Protein 15 -0.26 -0.78 0.73 0.74

9

Short SWCNT at 0.5 mg/LDNA 17 -0.48 -1.61 0.03 0.15Oxidative 16 -0.42 -1.34 0.16 0.30General 9 -0.36 -1.00 0.47 0.62Chemical 15 -0.24 -0.81 0.70 0.70

Short SWCNT at 2 mg/LDNA 17 -0.53 -1.69 0.02 0.09General 9 -0.45 -1.24 0.25 0.45Oxidative 16 -0.32 -0.98 0.50 0.66Chemical 15 -0.23 -0.72 0.79 0.79

Short SWCNT at 8 mg/LDNA 17 -0.50 -1.52 0.05 0.19Protein 15 -0.29 -0.85 0.67 1.00Oxidative 16 -0.19 -0.56 0.92 1.00General 9 -0.16 -0.43 0.99 0.99

Short SWCNT at 32 mg/LDNA 17 -0.59 -1.66 0.01 0.03Protein 15 -0.40 -1.06 0.41 0.60Oxidative 16 -0.23 -0.62 0.92 0.91

SWCNT-COOH at 0.031 mg/LProtein 15 -0.50 -2.02 0.01 0.01General 9 -0.26 -0.87 0.62 0.62

SWCNT-COOH at 0.125 mg/LGeneral 9 -0.44 -1.18 0.27 1.00Chemical 15 -0.33 -1.01 0.44 1.00Oxidative 16 -0.32 -0.97 0.51 0.85DNA 17 -0.26 -0.80 0.71 0.88Protein 15 -0.23 -0.68 0.83 0.82

SWCNT-COOH at 0.5 mg/LDNA 17 -0.50 -1.73 0.02 0.09General 9 -0.31 -0.91 0.58 1.00Chemical 15 -0.21 -0.72 0.79 1.00Protein 15 -0.19 -0.64 0.87 1.00Oxidative 16 -0.19 -0.63 0.87 0.88

SWCNT-COOH at 2 mg/LDNA 17 -0.41 -1.37 0.14 0.39Protein 15 -0.35 -1.15 0.33 0.46General 9 -0.28 -0.77 0.77 0.75

SWCNT-COOH at 8 mg/LDNA 17 -0.66 -2.06 0.00 0.00Protein 15 -0.26 -0.81 0.69 1.00General 9 -0.26 -0.70 0.82 0.82

SWCNT-COOH at 32 mg/LDNA 17 -0.69 -1.78 0.00 0.01Protein 15 -0.39 -0.99 0.51 1.00

10

Oxidative 16 -0.32 -0.81 0.76 1.00General 9 -0.26 -0.60 0.94 0.93

SWCNT-OH at 0.031 mg/LGeneral 9 -0.62 -1.81 0.01 0.03Oxidative 16 -0.39 -1.35 0.17 0.22DNA 17 -0.20 -0.72 0.81 0.80

SWCNT-OH at 0.125 mg/LGeneral 9 -0.58 -1.72 0.02 0.08DNA 17 -0.40 -1.41 0.12 0.24Protein 15 -0.31 -1.06 0.40 0.53Chemical 15 -0.20 -0.70 0.82 0.81

SWCNT-OH at 0.5 mg/LProtein 15 -0.37 -1.31 0.18 0.87General 9 -0.38 -1.14 0.28 0.75Oxidative 16 -0.19 -0.69 0.83 1.00DNA 17 -0.15 -0.56 0.94 1.00Chemical 15 -0.14 -0.49 0.97 0.97

SWCNT-OH at 2 mg/LDNA 17 -0.53 -1.81 0.01 0.05Protein 15 -0.27 -0.91 0.58 1.00General 9 -0.25 -0.71 0.84 1.00Oxidative 16 -0.14 -0.49 0.98 0.97

SWCNT-OH at 8 mg/LDNA 17 -0.70 -1.95 0.00 0.00General 9 -0.32 -0.79 0.74 1.00Protein 15 -0.25 -0.69 0.84 0.84

SWCNT-OH at 32 mg/LDNA 17 -0.72 -1.86 0.00 0.00Protein 15 -0.49 -1.23 0.21 0.30Oxidative 16 -0.38 -0.94 0.60 0.58

Metallic SWCNT at 0.0078 mg/LGeneral 9 -0.55 -1.59 0.04 0.10Oxidative 16 -0.37 -1.31 0.18 0.17

Metallic SWCNT at 0.031 mg/LDNA 17 -0.37 -1.18 0.28 0.85Oxidative 16 -0.33 -1.03 0.44 0.67General 9 -0.36 -0.94 0.55 0.54

Metallic SWCNT at 0.125 mg/LOxidative 16 -0.39 -1.23 0.23 0.71DNA 17 -0.34 -1.09 0.37 0.57Protein 15 -0.22 -0.70 0.82 0.82

Metallic SWCNT at 0.5 mg/LOxidative 16 -0.41 -1.27 0.21 0.63DNA 17 -0.39 -1.25 0.22 0.34General 9 -0.43 -1.12 0.33 0.34

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Metallic SWCNT at 2 mg/LGeneral 9 -0.47 -1.26 0.19 0.88DNA 17 -0.35 -1.13 0.31 0.66Oxidative 16 -0.29 -0.91 0.58 0.77Chemical 15 -0.23 -0.71 0.77 0.79

Metallic SWCNT at 8 mg/LDNA 17 -0.47 -1.41 0.09 0.50General 9 -0.44 -1.15 0.31 0.74Chemical 15 -0.28 -0.83 0.67 1.00Oxidative 16 -0.25 -0.76 0.77 0.96Protein 15 -0.21 -0.62 0.89 0.90

Semiconducting SWCNT at 0.0078 mg/LOxidative 16 -0.33 -1.34 0.14 0.45Protein 15 -0.31 -1.22 0.24 0.34General 9 -0.32 -1.04 0.37 0.40

Semiconducting SWCNT at 0.031 mg/LGeneral 9 -0.46 -1.37 0.15 0.54Protein 15 -0.36 -1.30 0.19 0.36Chemical 15 -0.29 -1.03 0.43 0.56DNA 17 -0.25 -0.89 0.57 0.58

Semiconducting SWCNT at 0.125 mg/LDNA 17 -0.34 -1.29 0.19 0.54Chemical 15 -0.28 -1.00 0.45 0.67Protein 15 -0.27 -0.96 0.51 0.50

Semiconducting SWCNT at 0.5 mg/LDNA 17 -0.34 -1.22 0.26 0.97Protein 15 -0.33 -1.18 0.27 0.55General 9 -0.32 -0.94 0.54 0.70Oxidative 16 -0.19 -0.70 0.83 0.84

Semiconducting SWCNT at 2 mg/LChemical 15 -0.38 -1.37 0.14 0.40DNA 17 -0.22 -0.86 0.62 0.94Protein 15 -0.16 -0.56 0.94 0.95

Semiconducting SWCNT at 8 mg/LOxidative 16 -0.49 -1.57 0.06 0.15Protein 15 -0.46 -1.43 0.10 0.16DNA 17 -0.26 -0.84 0.68 0.66

Note: a FDR: false discovery rate, indicative of probability that a protein set with a given NES represents a false positive finding. An enrichment with FDR < 25% is defined as significant based on GSEA, and FDR of 25% indicates that the result is likely to be valid 3 out of 4 times.

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Table S3. Overrepresented (p-value < 0.05) biological categories based on GO databases for a 2 h exposure with unmodified and functionalized SWCNTs at 32 mg/L, and metallic and semiconducting SWCNTs at 8 mg/L in yeast cells, employing the selected stress library as the reference set.

Category p-value Names of observed markers in category a Number of markers annotated by given term in reference set

Number of makers annotated by given term in test set

Long SWCNT at 32 mg/LGO Biological Processes

cellular response to stress [GO:0033554]

0.0049 YBP1; OGG1; GRX1; MAG1; PHR1; XRS2; MSH2; MRE11; HSP78; TRX1; SLN1; TRX3; RAD4; RAD9; MSN2; YAP1; CCP1; HAC1; CTT1; CHK1; YKU70; GRX2; UNG1; HOG1; HSP12; RAD51; HSP104; NTG2

34 28

cellular response to stimulus [GO:0051716]

0.0049 YBP1; OGG1; GRX1; MAG1; PHR1; XRS2; MSH2; MRE11; HSP78; TRX1; SLN1; TRX3; RAD4; RAD9; MSN2; YAP1; CCP1; HAC1; CTT1; CHK1; YKU70; GRX2; UNG1; HOG1; HSP12; RAD51; HSP104; NTG2

34 28

response to stress [GO:0006950]

0.0093 YBP1; OGG1; GRX1; MAG1; GSH1; PHR1; XRS2; MSH2; MRE11; HSP78; UBC1; TRX1; SLN1; TRX3; RAD4; RAD9; MSN2; YAP1; CCP1; HAC1; CTT1; HSP42; CHK1; UTH1; YKU70; GRX2; UNG1; HOG1; HSP12; RAD51; UBC5; HSP104; TPS1; NTG2; TPS2; SOD2

47 36

cellular process [GO:0006259]

0.0369 YBP1; CCS1; OGG1; GRX1; MAG1; GSH1; TPO1; PHR1; XRS2; MSH2; MRE11; HSP78; UBC1; TRX1; ATG1; SLN1; TPK2; TRX3; RAD4; RAD9; MSN2; YAP1; CCP1; HAC1; CTT1; BPT1; HSP42; CHK1; UTH1; GSH2; YKU70; PDR1; GRX2; UNG1;

70 48

13

HOG1; CDC28; ATM1; OXA1; HSP12; RAD51; QDR3; UBC5; HSP104; TPS1; NTG2; TPS2; SOD2; CDC48

response to DNA damage stimulus [GO:0006974]

0.0488 OGG1; MAG1; PHR1; XRS2; MSH2; MRE11; RAD4; RAD9; CHK1; YKU70; UNG1; RAD51; NTG2

15 13

GO Cellular Componentsmacromolecular complex [GO:0032991]

0.033 XRS2; MSH2; MRE11; UBC1; ATG1; TPK2; RAD4; HSP42; YKU70; CDC28; UBC5; TPS1; TPS2; CDC48

16 14

protein complex [GO:0043234]

0.033 XRS2; MSH2; MRE11; UBC1; ATG1; TPK2; RAD4; HSP42; YKU70; CDC28; UBC5; TPS1; TPS2; CDC48

16 14

Short SWCNT at 32 mg/LGO Biological Processes

macromolecule modification [GO:0043412]

0.0219 CHK1; UBC8; TRX1; MAG1; SLN1; CDC28; IRE1; HOG1; PHR1; ATG1; GRX1; TPK2; UBC5; UBC1; TPK1

17 15

post-translational protein modification [GO:0043687]

0.0244 CHK1; UBC8; SLN1; CDC28; IRE1; HOG1; PHR1; ATG1; TPK2; UBC5; UBC1; TPK1

13 12

phosphorylation [GO:0016310]

0.028 CHK1; SLN1; CDC28; IRE1; HOG1; ATG1; TPK2; TPK1 8 8

protein amino acid phosphorylation [GO:0006468]


phosphorus metabolic process [GO:0006793]


phosphate metabolic process


14

[GO:0006796]protein modification process [GO:0006464]

0.033 CHK1; UBC8; TRX1; SLN1; CDC28; IRE1; HOG1; PHR1; ATG1; GRX1; TPK2; UBC5; UBC1; TPK1

16 14

GO Molecular Functionstransferase activity, transferring phosphorus-containing groups [GO:0016772]

0.0105 CHK1; SLN1; CDC28; IRE1; MRE11; HOG1; ATG1; TPK2; RAD30; TPK1

10 10

kinase activity [GO:0016301]

0.0172 CHK1; SLN1; CDC28; IRE1; MRE11; HOG1; ATG1; TPK2; TPK1 9 9

phosphotransferase activity, alcohol group as acceptor [GO:0016773]


protein kinase activity [GO:0004672]


protein serine/threonine kinase activity [GO:0004674]

0.0451 CHK1; CDC28; IRE1; HOG1; ATG1; TPK2; TPK1 7 7

SWCNT-COOH at 32 mg/LGO Biological Processes

negative regulation of biological process

0.0205 RAD9; CDC28; UBC8; CHK1; UTH1; YKU70; MSH2; PDR1; HOG1; PDR3

10 10

15

[GO:0048519]negative regulation of cellular process [GO:0048523]

0.0205 RAD9; CDC28; UBC8; CHK1; UTH1; YKU70; MSH2; PDR1; HOG1; PDR3

10 10

negative regulation of cellular metabolic process [GO:0031324]

0.0313 RAD9; CDC28; UBC8; CHK1; YKU70; MSH2; PDR1; HOG1; PDR3

9 9

negative regulation of cellular biosynthetic process [GO:0031327]


9 9

negative regulation of biosynthetic process [GO:0009890]


9 9

negative regulation of metabolic process [GO:0009892]


9 9

regulation of RNA metabolic process [GO:0051252]

0.0318 MRE11; RAD9; CDC28; SLN1; UTH1; YKU70; MSN2; MSH2; PDR1; HOG1; YAP1; PDR3; SKN7

14 13

regulation of transcription, DNA-dependent [GO:0006355]

0.0318 MRE11; RAD9; CDC28; SLN1; UTH1; YKU70; MSN2; MSH2; PDR1; HOG1; YAP1; PDR3; SKN7

14 13

negative regulation of macromolecule

0.0473 RAD9; CDC28; CHK1; YKU70; MSH2; PDR1; HOG1; PDR3 8 8

16

biosynthetic process [GO:0010558]negative regulation of macromolecule metabolic process [GO:0010605]


negative regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process [GO:0045934]


negative regulation of nitrogen compound metabolic process [GO:0051172]


cell cycle [GO:0007049]

0.0473 MRE11; RAD9; CDC28; CHK1; UTH1; RAD51; CDC48; TPK1 8 8

GO Cellular Componentsmacromolecular complex [GO:0032991]

0.0146 MRE11; XRS2; RAD4; ATG1; CDC28; HSP42; KAR2; TPS1; YKU70; MSH2; UBC1; UBC5; CDC48; TPK1; TPK2

16 15

protein complex [GO:0043234]

0.0146 MRE11; XRS2; RAD4; ATG1; CDC28; HSP42; KAR2; TPS1; YKU70; MSH2; UBC1; UBC5; CDC48; TPK1; TPK2

16 15

nuclear part [GO:0044428]

0.0473 MRE11; XRS2; RAD4; YKU70; MSH2; TOP2; RAD51; YAP1 8 8

SWCNT-OH at 32 mg/L

17

GO Biological Processesresponse to stimulus [GO:0050896]

0.0342 RAD9; OGG1; MRE11; XRS2; MAG1; UBC5; CTT1; HSP104; UTH1; RAD4; PHR1; SOD2; GRX2; PDR1; CHK1; HSP42; MSN2; HSP78; GSH1; GRX1; YBP1; TRX1; UBC1; NTG2; PDR5; KAR2; MSH2; HOG1; RAD30; HAC1; SLN1; TPS1; PDR3; TRX3; YKU70; YCF1

52 36

negative regulation of biological process [GO:0048519]

0.045 RAD9; UBC8; UTH1; PDR1; CHK1; MSH2; HOG1; PDR3; YKU70 10 9

negative regulation of cellular process [GO:0048523]

0.045 RAD9; UBC8; UTH1; PDR1; CHK1; MSH2; HOG1; PDR3; YKU70 10 9

autophagy [GO:0006914]

0.0478 UBC5; UBC8; UTH1; RAD4; ATG1; TPK1 6 6

Metallic SWCNT at 8 mg/LGO Biological Processes

DNA metabolic process [GO:0006259]

0.0079 OGG1; PHR1; RAD4; RAD9; XRS2; RAD51; MAG1; NTG2; UNG1; RAD30; MSH2; YKU70; MRE11; NTG1; TOP2; CHK1

16 16

response to DNA damage stimulus [GO:0006974]

0.0111 OGG1; PHR1; RAD4; RAD9; XRS2; RAD51; MAG1; NTG2; UNG1; RAD30; MSH2; YKU70; MRE11; NTG1; CHK1

15 15

DNA repair [GO:0006281]

0.0156 OGG1; PHR1; RAD4; RAD9; XRS2; RAD51; MAG1; NTG2; UNG1; RAD30; MSH2; YKU70; MRE11; NTG1

14 14

nucleic acid metabolic process [GO:0090304]

0.0295 HAC1; OGG1; PHR1; RAD4; RAD9; XRS2; RAD51; HOG1; YAP1; MAG1; NTG2; SKN7; UNG1; PDR1; RAD30; MSH2; YKU70; MRE11; NTG1; TOP2; PDR3; CHK1

24 22

GO Cellular Components

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nucleus [GO:0005634]

0.0413 CCS1; HAC1; OGG1; TPK2; PHR1; RAD4; RAD9; XRS2; RAD51; TPK1; HOG1; YAP1; MAG1; NTG2; SKN7; UNG1; PDR1; GRX1; CDC48; RAD30; NMA111; MSH2; YKU70; MRE11; HSP26; NTG1; TRX1; HSP104; SOD1; TOP2; PDR3; CHK1

37 32

Semiconducting SWCNT at 8 mg/LGO Biological Processes

response to stimulus [GO:0050896]

0.0073 KAR2; TRX1; HSP42; CTT1; PDR1; MSH2; TRX3; MAG1; GRX1; GSH1; MSN2; SLN1; HSP104

52 13

response to chemical stimulus [GO:0042221]

0.0105 KAR2; TRX1; CTT1; PDR1; TRX3; GRX1; GSH1; MSN2; SLN1 27 9

response to oxidative stress [GO:0006979]

0.0126 TRX1; CTT1; TRX3; GRX1; GSH1; MSN2; SLN1 18 7

response to hydrogen peroxide [GO:0042542]

0.0164 CTT1; GSH1; SLN1 4 3

response to stress [GO:0006950]

0.0173 KAR2; TRX1; HSP42; CTT1; MSH2; TRX3; MAG1; GRX1; GSH1; MSN2; SLN1; HSP104

47 12

heat acclimation [GO:0010286]

0.0296 MSN2; HSP104 2 2

cellular response to extracellular stimulus [GO:0031668]

0.0296 CTT1; MSN2 2 2

cellular response to external stimulus [GO:0071496]

0.0296 CTT1; MSN2 2 2

cell communication 0.0296 CTT1; MSN2 2 2

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[GO:0007154]response to water [GO:0009415]

0.0296 CTT1; MSN2 2 2

response to external stimulus [GO:0009605]

0.0296 CTT1; MSN2 2 2

response to extracellular stimulus [GO:0009991]

0.0296 CTT1; MSN2 2 2

electron transport chain [GO:0022900]

0.0366 TRX1; TRX3; GRX1 5 3

cell redox homeostasis [GO:0045454]

0.0366 TRX1; TRX3; GRX1 5 3

cellular response to oxidative stress [GO:0034599]

0.0469 TRX1; CTT1; TRX3; GRX1; MSN2 13 5

GO Molecular Functionsdisulfide oxidoreductase activity [GO:0015036]

0.0366 TRX1; TRX3; GRX1 5 3

oxidoreductase activity, acting on sulfur group of donors [GO:0016667]

0.0366 TRX1; TRX3; GRX1 5 3

oxidoreductase 0.0473 TRX1; CTT1; TRX3; GRX1 9 4

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activity [GO:0016491]

Note: a: observed markers indicate proteins up-regulated with PELIORF > 1.5.

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Quantitative Toxicogenomics assay Lengths, Functional G ... · Membrane, cell wall and cell...

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