EMBO/sd-character-level-ner huggingface dataset:
Figure 3(A) Predicted binding sites for miR-483-3p/-5p on the 3'UTR of mRNAs as indicated. PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 24 hr. Expression levels of miR-483-3p/-5p measured by qPCR Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 24 hr. Expression levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 mRNA were measured by qPCR Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 24 hr. Expression levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 protein were measured by Western blot Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups (E) Bovine aortic ECs were transfected with a luciferase reporter fused with the 3'UTR of TGF-β (Luc-TGF-β WT), TGFBR2 (Luc-TGFBR2 WT), IL-1β (Luc-IL-1β WT) or ET-1 (Luc-ET-1 WT) or a binding site mutation (Luc-TGF-β Mut, Luc-TGFBR2 Mut, Luc-IL-1β Mut, ET-1-Mut), then infected with Lenti-pre-miR-483 for additional 36 hr. Luciferase activity was measured. Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 36 hr. The Ago1- or Ago2-associated miRNAs and mRNAs were enriched by immunoprecipitation with anti-Ago1 or anti-Ago2. Levels of miR-483-3p/-5p mRNA were detected by qPCR and normalized to those of Ago1 or Ago2 protein. Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups PAECs were infected with Lenti-pre-miR-483 or Lenti-null for 36 hr. The Ago1- or Ago2-associated miRNAs and mRNAs were enriched by immunoprecipitation with anti-Ago1 or anti-Ago2. Levels of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1 mRNA were detected by qPCR and normalized to those of Ago1 or Ago2 protein. Data information: Values are expressed as mean ± SEM from 3 independent experiments. Statistical test: t-test (*P < 0.05 between the indicated groups
Figure 5MITOL added polyubiquitin chains to K481 of IRE1α. Lysates of HEK293 cells transfected with each lysine mutant of IRE1α and indicated vectors were immunoprecipitated with anti-FLAG antibody, followed by immunoblotting with indicated antibodies. 481: K481R, 545: K545R, 568: K568R. IRE1α K481R interacted with MITOL. Lysates of HEK293 cells transfected with indicated vectors were immunoprecipitated with anti-FLAG antibody, followed by immunoblotting with indicated antibodies. Overexpression of IRE1α K481R induced apoptosis. MEFs were transfected with indicated vectors. After 24 hours, these cells were stained with Annexin V-FITC Overexpression of IRE1α K481R induced apoptosis. or subjected by immunoblotting with indicated antibodies (D). Enhanced RIDD activity in IRE1α K481R. MEFs were transfected with indicated vectors 24 hours prior to analysis (E, F). The RIDD activity was measured by qRT-PCR. Hyper-oligomerization of IRE1α K481R. MEFs were transfected with IRE1α-GFP or IRE1α K481R-GFP. After 24 hours, these cells were exposed with Tu for indicated periods and GFP signals were observed. The right panels show 5.5-fold magnification images of the boxed regions. Percentages of cells with IRE1α-foci were calculated from 100 cells by visual inspection in each independent experiment. Increased interaction of IRE1α K481R with BIM. Cells transfected with indicated vectors 24 hours prior to immunoprecipitation, followed by immunoblotting with indicated antibodies.
Figure 1A-C. Enzyme-linked immunosorbent assay (ELISA) of IL-6, TNF-α and IFN-β protein and real-time PCR analysis of IL-6, TNF-α and IFN-β mRNA in peritoneal macrophage isolated from wild type and RKIP-deficient mice treated with VSV (MOI,0.1) (A). A-C. Enzyme-linked immunosorbent assay (ELISA) of IL-6, TNF-α and IFN-β protein and real-time PCR analysis of IL-6, TNF-α and IFN-β mRNA in peritoneal macrophage isolated from wild type and RKIP-deficient mice treated with SEV (MOI,10) (B). A-C. Enzyme-linked immunosorbent assay (ELISA) of IL-6, TNF-α and IFN-β protein and real-time PCR analysis of IL-6, TNF-α and IFN-β mRNA in peritoneal macrophage isolated from wild type and RKIP-deficient mice transfected with poly(I:C) ( 1 μg/ml) (C). D. Fluorescence-activated cell sorting (FACS) and TCID50 (50% tissue culture infective dose) assessing the proliferation level of VSV. RAW264.7 cells line stably overexpressed flag-RKIP was infected with VSV-eGFP at MOI of 1 for the indicated time. The fusion protein fluorophore were analyzed by FACS. Then fresh medium with the VSV-eGFP infection was serially diluted on the monolayer of HEK293 cells for 3-7 days and TCID50 was measured. E. FACS analysis the infection of wild type and RKIP-deficient peritoneal macrophage infected with VSV-eGFP at MOI of 1. The fresh medium with the VSV-eGFP infection 9 hr were collected for TCID50 assessing.
Figure 7A. The ratios of GFP-positive HK1 cells transfected with the ZAP-, DDX17- and DCP2-specific siRNAs or the siNC control were quantified using FACS. At 24 h post siRNA transfection, the protein level of indicated genes was determined by western blot analysis. ACTB was used as loading control. B. The GFP-positive cells in CNE2EBV cells transfected with the ZAP-, DDX17-, and DCP2-specific siRNAs or the control siRNA following EBV reactivation, were quantified using FACS. At 24 h post siRNA transfection, the protein level of indicated genes was determined by western blot analysis. ACTB was used as loading control. C. The relative number of EBV copies in C666 cells transfected with the ZAP-, DDX17- and DCP2-specific siRNAs or the siNC control was measured using qPCR. At 24 h post siRNA transfection, the protein level of indicated genes was determined by western blot analysis. ACTB was used as loading control. D. The relative mRNA levels of BZLF1 and BRLF1 in C666 cells transfected with the YTHDF1-specific siRNAs (siY1-1 and siY1-2) or the siNC control. E. The ratio of endogenous 5'-capped BZLF1 and BRLF1 mRNAs in C666 cells at 24 h post transfection with the YTHDF1-specific siRNAs or the siNC control. The ratios of endogenous 5'-capped mRNAs were quantified by dividing the abundance of XRN1-resistant transcripts with the total amount of transcripts. F. The relative mRNA levels of BZLF1 and BRLF1 in C666 cells transfected with YTHDF1-specific siRNAs and XRN1-specific siRNAs. The C666 cells were co-transfected with YTHDF1-specific siRNAs and XRN1-specific siRNAs for 24 h. The mRNA levels were determined using qPCR. G. The relative enrichment of BZLF1 and BRLF1 mRNAs by ZAP, DDX17, or DCP2 in CNE2EBV cells following EBV reactivation. CNE2EBV cells were transfected with plasmids encoding myc-ZAP, myc-DDX17, myc-DCP2, or vector control. At 24 h post transfection, the cells were treated with TPA (30 ng/ml) and NaB (2 mM) for 24 h. The RIP assays were performed using Myc-beads. The fold enrichment was determined by calculating the 2-ΔCt of the RIP sample relative to the input sample. H. Determination of the EBV infection efficiency in HK1 cells transfected with the XRN1-specific siRNA or the siNC control. After 24 h of siRNA transfection, HK1 cells were infected with EBV and analyzed by FACS at 24 hpi. I. The relative mRNA levels of BZLF1 and BRLF1 in the EBV-infected HK1 cells transfected with the XRN1-specific siRNA (siXRN1) or the siNC control at 24 hpi. All gene expression levels were normalized to the housekeeping gene ACTB.
Criteria of final SNP selection in the phenotype-based genetic association study (PGAS) approach – Standard operating procedure (SOP).Figure 3(A-B) A total of 13 SNPs pre-selected according to the SOP presented in Fig 2 underwent PGAS screening as exemplified here: (A) PAUSS association pattern of an exemplary fictitious autosomal (upper panel) and a sex-chromosomal (lower panel) SNP which are eligible for the accumulation model. The genotype associated with the highest average PAUSS (in this example CC) is the 'proautistic genotype' (indicated by the black arrow) and is assigned a score of 1. The heterozygous genotype is assigned a score of 0.5 and the homozygous genotype associated with the lowest PAUSS receives a score of 0. Please note that the difference between genotypes does not have to be statistically significant. (B) PAUSS association pattern of an exemplary fictitious autosomal (upper panel) and a sex-chromosomal (lower panel) SNP which would not be selected for the accumulation model because of unclear phenotypical/biological relevance. (C-D) The specificity of the association of the 8SNP accumulation model with an autistic phenotype (as determined using PAUSS; compare Fig 4B) is controlled by applying an unrelated (or 'non-sense') phenotype, e.g. delusional-depression: (C) Intercorrelation pattern of single items included in the delusional-depression composite score, used here as example control phenotype. Cronbach's alpha is presented as measure of internal consistency. (D) The delusional-depression composite score is not associated with the number of proautistic genotypes of the 8SNP risk model in the discovery sample.
Cx43 modulates the selective sorting of miRNAs into extracellular vesicles.Figure 1A. EV produced by HEK293 cells expressing or not Cx43 (EVCx43+ or EVCx43-) were purified by differential ultracentrifugation. miRNAs expression profile analysis in EVCx43+ (represented as fold increase over EVCx43-). B. Pathway enrichment analysis for the predicted targets of the over-represented miRNAs in Cx43-containing EV. C. HEK293 cells were incubated with 5 µg of purified EVCx43- or EVCx43+ for 24 h, in the presence or absence of Bafilomycin A1 (Baf) in the last 6 h. The levels of LC3 were analyzed by WB and are depicted on graph (LC3-II; n=4 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs. D. miRNA-centered regulatory network established by the miRNAs enriched in Cx43-containing EV. The figure represents predicted targets that are simultaneously regulated by 3 or more of the selected miRNAs. The size of the symbols is proportional to the number of established functional connections. miRNA-regulatory are represented by grey edges. Protein-protein interactions obtained from STRING database are depicted in black lines. E. HEK293 cells were incubated with EVCx43- or EVCx43+ for 24 h before WB analysis of ATP2A2/SERCA2, a predicted target of miRNAs enriched in Cx43-containing EV. Graph depicts quantification of ATP2A2/SERCA2 levels (n=4 biological replicates). Data information: p-values were derived by Mann-Whitney test. Bars and error bars indicate mean ± SD in all graphs.
Figure 2Each panel represents immunoblots of whole cell lysates stained with an anti-HA antibody detecting arrestin. In the left panels GPCRs were combined with βarr1 variants, in the right panels with βarr2 variants. Residues replaced by Bpa are indicated above each lane. Covalent arrestin-receptor complexes are expected between 100-200 kDa, considering the size of the receptors (V2R 41.5 kDa, PTH1R 63.8 kDa, CRF1R, 46.3 kDa) and their glycosylation. A PTH1R, agonist PTH(1-34) B CRF1R, agonist Urocortin 1 (Ucn1) C V2R, agonist arginine-vasopressin (AVP) D No receptor.
Figure 4(A) Secondary structures of the anticodon loop of three types of tRNAPhe(GAA) s: tRNAPhe(GAA), △ftsj1_tRNAPhe(GAA), and m1G37_tRNAPhe(GAA). (B, C) Quantification of the Cm/A and Gm/A of tRNAPhe(GAA), △ftsj1_tRNAPhe(GAA), and m1G37_tRNAPhe(GAA) after incubation with FTSJ1, WDR6, and FTSJ1-WDR6 by UPLC-MS/MS analysis, respectively. Error bars represent the standard deviation of three independent experiments. n.d., not detected. (D) UPLC-MS/MS analysis of 2'-O-methylation of m1G37_tRNAPhe(GAA), -G34A, -G34C and G34U after incubation with FTSJ1-WDR6. 2 μL of Gm (1 ng/mL), Am (1 ng/mL), Cm (1 ng/mL) and Um (5 ng/mL) standards were injected to UPLC-MS/MS as control. cps, counts per second.
Fig.Figure 3(A) Schematic representation of the strategy used for consecutive stress treatment. (B) Pattern correlation used to find proteins that accumulate upon ABA/NAA treatment and are removed in WT but not in atg2 after swapping to flg22/6-BA. Protein clusters obtained after quantitative proteomics of WT (green) and atg2-2 (magenta) samples treated as described (C) Protein cluster fitting the pattern displayed (D) Protein cluster for proteins that accumulate to higher levels in atg2 than WT upon treatment with flg22. Protein clusters obtained after quantitative proteomics of WT (green) and atg2-2 (magenta) samples treated as described (E) Protein cluster of proteins which accumulate upon NAA treatment and are removed in WT but not in atg2 after swapping to 6-BA (F) Protein cluster for proteins that accumulate to higher levels in atg2 than WT upon treatment with 6-BA.
a) MPTP administration decreases the numbers of tyrosine hydroxylase (TH)- and cresyl violet (CV)-positive neurons in the substantia nigra.figf5(a) MPTP administration decreases the numbers of tyrosine hydroxylase (TH)- and cresyl violet (CV)-positive neurons in the substantia nigra. Representative images of tyrosine hydroxylase-stained brain sections are shown. Right panels show quantified data as means ± s.e.m.; n=9 for tyrosine hydroxylase and n=3 for cresyl violet. (b) MPTP administration upregulates the levels of LC3-II and Thr 145-phosphorylated EndoB1 in the midbrain. Lower panels show quantified data as means ± s.e.m.; n=3. (c) Knockdown of EndoB1 or Cdk5 inhibits MPP+-induced autophagy in cultured neurons. Data are means ± s.e.m.; n=5. (d) Cdk5 mediates the MPP+-induced EndoB1 phosphorylation at Thr 145 and the MPP+-induced increase in the LC3-II level in neurons. (e) Overexpression of EndoB1T145A attenuates MPP+-induced autophagy in neurons. Data are means ± s.e.m.; n=7. (f) MPTP fails to increase LC3-II and Thr 145-phosphorylated EndoB1 levels in the midbrain of p35−/− mice. The concomitant reduction in tyrosine hydroxylase level triggered by MPTP injection is also markedly attenuated. Right panels show quantified data as means ± s.e.m.; n=3. Uncropped images of blots are shown in Supplementary Fig. S8.
Model of Elongator’s tRNA modification reaction.Figure 6A. Overview of holoElongator and individual domains important for the interaction of Elp123 with Elp456. Elp1 (orange), Elp2 (yellow), Elp3 (pink), Elp4 (green), Elp5 (blue) and Elp6 (sand) are shown in surface representation to indicate the topological nature of our model. Individual domains are labeled. B. Same as A but tilted view to highlight the active site cavity (left). Close up view of the active site in which all known tRNA binding sites and a region of Elp2 important for tRNA modification activity are highlighted. Individual structures of the subunits are shown in cartoon and surface representation. C. Close up view on the localization of Elp3 and the orientation of its KAT and SAM domain in relation to Elp1 and Elp2. D. Close up view on the relative spatial orientation of the conserved basic patch in Elp2 and the potential interaction site between Elp456 and a region of Elp2 important for tRNA modification activity.
Figure 6Confocal analysis of co-localization of VISP1-GFP and RFP-SGS3 with the CFP-NbATG8f-labelled autophagic bodies in N. benthamiana leaves. The infiltrated leaves were treated with 100 µM E64d or DMSO at 48 hpi and examined at 60 hpi. Arrow heads indicate autophagic bodies. Scale bar = 10 μm. Confocal analysis of co-localization of CFP-NbATG8f-labelled autophagic bodies with the VISP1-YN and SGS3-YC bodies in N. benthamiana leaves. The infiltrated leaves were treated with 100 µM E64d or DMSO at 48 hpi and examined for imaging at 60 hpi. Scale bar = 20 μm. Effect of VISP1-Flag and the autophagy inhibitor 3-MA on accumulation of SGS3-Flag and SGS3ΔCC-Flag in N. benthamiana leaves. The co-infiltrated leaves were treated with 3-MA (10 mM) or buffer at 48 hpi and were harvested for western blotting 12 h later. Accumulation of AtSGS3 transcript was analyzed by RT-PCR. Effect of VISP1mARM-Flag on accumulation of SGS3-Flag. Effect of VISP1mUIM-Flag on accumulation of SGS3-Flag. Confocal analysis of effect of VISP1-Flag VISP1mARM-Flag, and VISP1mUIM-Flag on RDR6-YN and SGS3-YC formed bodies in N. benthamiana leaves at 60 hpi. EV: empty vector. Scale bar = 20 μm.   Numbers of RDR6-YN and SGS3-YC formed bodies per 10 cells in E were used for quantification. Data points represent means of three biological repeats. Error bars indicate SD. Letters indicate significant differences (ANOVA, P < 0.05).   Western blotting showing accumulation of proteins as indicated in the samples of E. Western blotting detecting accumulation of the endogenous SGS3 protein in leaves of 2-week-old Col-0, VISP1OE, visp1, and sgs3-1 Arabidopsis plants with anti-SGS3 antibodies.   Western blotting detecting accumulation of the endogenous SGS3 protein in leaves of 2-week-old Col-0, VISP1OE, VISP1mUIM/OE, and VISP1mARM/OE Arabidopsis plants.   Western blotting detecting accumulation of the endogenous SGS3 protein in 2-week-old VISP1-overexpressing Col-0, atg5-1, and atg7-1 mutants.
Figure 7A. The mutations in CDK sites on Apc3-loop reduces phosphorylation of T532 on Apc1. The purified recombinant WT or a mutant APC/C with mutations at nine CDK sites in Apc3-loop (3-9A) was incubated with APC/C-depleted (ΔAPC) anaphase extracts supplemented with non-degradable cyclin B at 23˚C for 60 min. The APC/C was recovered with Apc3 monoclonal antibody (AF3.1) beads, and the phosphorylation status of T532 in Apc1 was analysed by SDS-PAGE and immunoblotting with phospho-specific (pT532) or Apc1 (pan-Apc1) antibodies. B. Similar to (A), but the experiments were performed at three time points, 45 min, 60 min or 75 min in anaphase extracts. Quantification of phosphorylation levels of T532 are shown. The intensities of pT532 signals in WT at each time point (45 min, 60 min or 75 min) were arbitrarily set to 1.0. The level of T532-phosphorylation was normalised to pan-Apc1. Error bars, SEM from three independent experiments. C. PP2A-B56 preferentially binds to T532-phoshorylated Apc1-loop500. Flag-tagged B56γ was incubated with the MBP-fused Apc1-loop500 phosphorylated by Cdk2/cyclin A. The bound proteins were recovered by anti-flag affinity M2 beads, separated by SDS-PAGE and detected by immunoblotting with phospho-specific (pT532), MBP or Flag antibody. The signals of a phospho-specific antibody (pT532) and MBP were pseudo-coloured (green; pT532, red; MBP) and overlaid (Overlay). D. A feedback control of APC/C by Plx1 and PP2A-B56 on Apc1-loop500. CDK phosphorylates Apc1-loop500 at T539 and S558 and promotes Plx1-binding onto Apc1-loop500 via its PBD. Two PBD interactions, possibly dimerisation of Plx1, may stabilise the complex between Plx1 and Apc1-loop500. Plx1-binding blocks PP2A-B56 recruitment to Apc1-loop500 and stimulates Apc3-loop phosphorylation, which may induce Cdk1-CyclinB-p9/Cks2 recruitment and subsequent Apc1-loop300 phosphorylation. Cdk1 recruited onto phosphorylated Apc3-loop promotes phosphorylation of T532, a residue important for the recruitment of PP2A-B56 on Apc1-loop500. PP2A-B56 recruitment promotes dissociation of Plx1 by competitive binding and by dephosphorylation of T532 and T539, which diminishes Plx1-mediated phosphorylation of Apc3-loop. PP2A-B56 may quickly dissociate from Apc1-loop500 once T532 is dephosphorylated, but Apc1-loop500 is phosphorylated again by Cdk1 while Cdk1 is active. The dynamic phosphorylation-dephosphorylation cycle may continue until Cdk1 is inactivated, allowing swift response of the APC/C during the cell cycle.
Figure 1(A) Quantification of AURKB transcripts in non-IPF lung derived resident-fibroblasts treated with indicated mitogens for 16hrs. *P < 0.05, ***P < 0.0005, and ****P < 0.00005, 1-way ANOVA, (n=4). (B) Quantification of AURKB gene transcripts in isolated fibroblasts from non-IPF and IPF lung stromal cell cultures. **P < 0.005, unpaired t-test, (n=6). (C) IPF and non-IPF lung sections were immunostained using AURKB antibody (n=4). Representative images were obtained at 40X magnification. Scale bar: 40µm. Dotted area: black; myofibroblastic core, blue; active fibrotic front. Arrows indicate AURKB positive cells. (D) Immunoblots of Aurkb and Aurka in total lung lysates of normal (CCSP/-) and fibrotic (CCSP/TGFα) mice fed with Dox for 6wks. Quantification was performed using phosphor imager software and normalization was done using loading control GAPDH. *P < 0.05, unpaired t-test, (n=4). (E) Immunostaining was performed using AURKB antibody in lung sections of control (CCSP/-) and TGFα (CCSP/TGFα) mice on Dox for 6wks (n=6). Representative images were obtained at 20X (low; Scale bar: 100µm) and 63X (high; Scale bar: 30µm) magnification. Dashed box indicates area of the section showing in high magnification. (F) Western blot analysis of Aurkb in total lung lysates from saline and bleomycin treated mice. Quantification was performed using phosphor imager software and normalization was done using loading control Gapdh. **P < 0.005, unpaired t-test, (n=4-5).
Prediction in clinical samples.Figure 6A. Rab25 expression correlates with glycogen levels in patienttumours. Total RNA and total cellular extracts, isolated from 31 ovarian cancer patient specimens, were subjected to Rab25 gene expression and glycogen content analysis using qPCR and glycogen assay, respectively. B-C. The Rab25 expression signature identifies patients with a poor prognosis. Ovarian cancer patients were classified as either mirroring the Rab25-associated gene expression signature (Rab25 signature) or not (non-Rab25 signature) using linear discriminant analysis in BRB tools, in two independent published ovarian datasets. Progression free survival curvesfor patients with advanced disease (Stage II to IV) are shown. Univariate analyses were plotted using Kaplan-Meier method and Coxplots used for multivariate analyses (co-variates included stage, grade, histology and residual disease).B. Tothill et al, 2008.C. Dressman et al, 2007. D. Prediction of breast cancer overall survival in two independent published breast datasets (upper panel) Pawitan et al, 2005 and (lower panel) Chin et al, 2006, based on Rab25-associated gene signature. Breast patient classification was determined by BRB tool class prediction function to identify patient with Rab25-associated gene expression signature (Rab25-signature) or without (non-Rab25 signature). All patients from the datasets were included in class prediction. E. Proposed model for the mechanism by which Rab25 regulates cellular bioenergetics.
Fig.Figure 4A T-ALL cells of n=19 patients were engrafted into mice, cryopreserved after harvesting and enriched for viable cells after defrosting. Then, they were subjected to the ATAC-sequencing. Patients P7, P8, P10, P59 were published previously B Projection of 19 T-ALLs in the PCA space of 2,823 signature OCRs discriminating T-cell developmental stages. C Deconvolution analysis by CIBERSORT trained on the 2,823 signature OCRs. Stacked columns represent the contribution of each developmental stage (indicated by color) to each leukemia patient (x-axis). D Chromatin accessibility as assessed by the number of ATAC peaks identified in the sorted populations of normal thymic T-cell precursors and in T-ALLs, respectively (n=10/19 patients have two biological replicates, n=9/19 patients have one replicate). Horizontal lines of the box plot indicate the median, lower and upper limits of each box correspond to the first and third quartiles (the 25th and 75th percentiles) and the lower and upper whiskers extend from min to max; pval=4.4e-08 (Kruskal-Wallis Test). E Heatmap representing the enrichment and depletion of binding motifs of top 50 TFs in OCRs of T-ALLs in comparison to healthy T-cell precursors. Patients on the x-axis; same order as in panel (C). Gray cells represent TFs having non-significant enrichment or depletion.