The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index; 5 of the 15 sources its claims cite were checked for support.
Subtype-specific 3D genome alteration in acute myeloid leukaemia
Open accessAbstract
Acute myeloid leukaemia (AML) represents a set of heterogeneous myeloid malignancies, and hallmarks include mutations in epigenetic modifiers, transcription factors and kinases 1 – 5 . The extent to which mutations in AML drive alterations in chromatin 3D structure and contribute to myeloid transformation is unclear. Here we use Hi-C and whole-genome sequencing to analyse 25 samples from patients with AML and 7 samples from healthy donors. Recurrent and subtype-specific alterations in A/B compartments, topologically associating domains and chromatin loops were identified. RNA sequencing, ATAC with sequencing and CUT&Tag for CTCF, H3K27ac and H3K27me3 in the same AML samples also revealed extensive and recurrent AML-specific promoter–enhancer and promoter–silencer loops. We validated the role of repressive loops on their target genes by CRISPR deletion and interference. Structural variation-induced enhancer-hijacking and silencer-hijacking events were further identified in AML samples. Hijacked enhancers play a part in AML cell growth, as demonstrated by CRISPR screening, whereas hijacked silencers have a downregulating role, as evidenced by CRISPR-interference-mediated de-repression. Finally, whole-genome bisulfite sequencing of 20 AML and normal samples revealed the delicate relationship between DNA methylation, CTCF binding and 3D genome structure. Treatment of AML cells with a DNA hypomethylating agent and triple knockdown of DNMT1 , DNMT3A and DNMT3B enabled the manipulation of DNA methylation to revert 3D genome organization and gene expression. Overall, this study provides a resource for leukaemia studies and highlights the role of repressive loops and hijacked cis elements in human diseases. Extensive genomic analyses of the chromatin architecture in acute myeloid leukaemia reveals several characteristics, including subtype-specific distal enhancers and silencers, that may represent new anticancer therapeutic targets.
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TL;DR
This study maps 3D genome organization in primary acute myeloid leukemia (AML) and identifies subtype-specific A/B compartment switches, TAD alterations, chromatin loops, and architectural stripes. It further shows that promoter-silencer loops and structural-variant-induced enhancer/silencer hijacking contribute to gene dysregulation, and that DNA hypomethylating treatment or DNMT triple knockdown can partially reverse AML-associated chromatin topology.
Key findings
- In 25 AML and 7 healthy donor samples, Hi-C identified recurrent and subtype-specific 3D alterations: on average 3.2% A-to-B and 2.9% B-to-A compartment switches versus HSPC; 391 of 622 curated COSMIC cancer/AML-related genes fell in altered TADs in at least one sample, with >100 recurrent.
- AML-specific loops averaged ~200 per AML sample; 42.4% were promoter-enhancer (P-E) and 11.2% promoter-silencer (P-S), with P-S loops accounting for 9.2% of all loops and averaging 169 kb. CRISPR deletion of an RTTN silencer increased RTTN expression 3-fold (p=5E-5), and CRISPRi de-repression of IKZF2-linked silencers increased IKZF2 expression >35-fold (P=0.00017).
- SV-induced neo-loops included enhancer hijacking (17.2% of neo-loops) and silencer hijacking (5.7%); CRISPRi screening of 74 neo P-E loops in Kasumi-1 cells identified 14 sgRNAs targeting 13 enhancers as significantly depleted, and hijacked silencer de-repression increased EXD1 and ALG10 expression by 5.97-fold and 2.70-fold, respectively.
- 5-AZA treatment reduced global methylation from 74% to 39%; 31.6% of AML-specific loops dissociated after treatment versus 2.5% of shared loops, and 55% of A-to-B altered compartments in an AML cell line were reversed to the A compartment.
Methods
- Primary samples: in situ Hi-C and RNA-seq in 32 primary samples (25 AML, 4 normal CD34+ HSPC, 3 PBMC), with ~600 million paired-end reads per Hi-C library; WGS at ~40x in 25 AML; ATAC-seq and CUT&Tag for H3K27ac, H3K27me3, and CTCF; WGBS in 18 AML and 2 PBMC at ~30X; 199 total genomic datasets.
- Functional validation: 4C-seq, 3D DNA FISH, HiChIP for H3K27me3, CRISPR deletion, CRISPRi/CRISPR activation, luciferase reporter assays, and a CRISPRi screen in Kasumi-1 cells; cell-line experiments in Kasumi-1, THP-1, HL60, U937, and K562.
- Perturbation: U937 cells treated with 0.5 μM 5-AZA for 12 days or subjected to inducible DNMT3A/3B/1 triple knockdown, followed by WGBS and Hi-C; computational analyses included Hi-C compartment/TAD/loop calling, NeoLoopFinder, stripe detection, and differential loop/compartment analyses.
Limitations
- The paper states that future experiments should aim to dissolve chromatin interactions without changing local chromatin status at cis-regulatory elements, and that phenotypic effects need deeper study, with animal models desirable.
- Evident from the text: the primary AML cohort is moderate in size (25 samples), and subtype-specific conclusions rest on small subgroups; functional validation of loops and hijacking is largely performed in AML cell lines rather than in vivo.
- Evident from the text: although the authors report that <4.8% of AML-specific loops were in CNV regions, structural variation and copy-number effects remain potential confounders in 3D genome analyses.
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Claims the paper makes
114 Own result · 24 Own method · 11 Own interpretation · 7 Not checked yet · 3 Partly supported · 2 No basis given · 1 Supported · accuracy not yet measured
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In the paper
“However, as shown in Extended Data Fig. 3c, the majority of TAD alterations did not affect the expression of genes, consistent with a recent study in multiple cancer types26.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > TAD alteration and gene expression
What the sources say
- Partly supportedcites [26] Akdemir, K. C. et al. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer. Nat. Genet. 52, 294–305 (2020). sourceExperimental — accuracy not yet measured
The Results section, “Most domain disruptions do not result in marked gene-expression changes” (page unavailable), reports that only 14% of the analyzed boundary-altering deletions coincided with a twofold expression change. This supports the claim that most did not coincide with a marked change, but it does not establish that most TAD alterations had no effect on gene expression at all. (LLM, conf=0.83)
plain- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Clustering analysis by Hi-CRep49 showed that 5-AZA treated and DNMT TKD cells were more similar to each other than the DMSO treated cells (Fig. 6e).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
What the sources say
- Supportedcites [49] Yang, T. et al. HiCRep: assessing the reproducibility of Hi-C data using a stratum-adjusted correlation coefficient. Genome Res. 27, 1939–1949 (2017). source
The citation identifies HiCRep as the method used for the citing paper’s clustering analysis. The source’s Results section (“Evaluating biological relevance by constructing cell lineages”) describes using HiCRep to assess similarities among cell types and construct a hierarchy. The 5-AZA, DNMT TKD, and DMSO comparison is the citing paper’s own result, attributed to its Figure 6e, not to this source. (LLM, conf=0.92)
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“We noticed that a cluster of samples all contained mutations in the KMT2B gene, which has not been used as a dominant AML subtyping classifier before.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Subtype-specific compartmentalization
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“The samples were clustered into different groups, which accurately reflected the AML genetic subtypes (Fig. 1c), such as RUNX1 and CEBPA mutations.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Subtype-specific compartmentalization
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, we observed other compartment switch regions unique to AML or AML subgroups, containing known AML gens such as POUA2F1, FGF13, and BCL11 (Extended Data Fig. 2c).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Subtype-specific compartmentalization
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, the A/B compartment switching regions also grouped by their genetic mutation profile (Fig. 1f).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Subtype-specific compartmentalization
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“We observed that CTCF binding sites in AML samples were hypomethylated (Extended Data Fig. 11c).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Altered DNA methylation and 3D genome
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In the paper
“Only less than 4.8% of the AML-specific loops were in the CNV regions (Extended Data Fig. 4a-b), suggesting that they were not confounded by copy number variations (CNVs).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > AML-specific chromatin loops
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In the paper
“We performed luciferase reporter assays to test the activity for five of them and all increased the luciferase expression (Fig. 4j).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Function of hijacked enhancers
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Deletion of this silencer increased the RTTN expression by 3 folds (Extended Data Fig. 7g, p=5E-5), dramatically slowed cell proliferation (Extended Data Fig. 7h), and decreased the sizes of the colonies by colony formation assay (Extended Data Fig. 7i-j).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Validating promoter-silencer loops
plainstates a causeSingle case- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 34
- Probably not a substantial claim. 29
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We identified 391 out of the 622 curated COSMIC cancer-related and AML-related genes located inside the altered TADs in at least one sample, and more than 100 are recurrent across multiple samples (Extended Data Fig. 3b)4,24,25.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > TAD alteration and gene expression
What the sources say
- Partly supportedcites [4] Papaemmanuil, E. et al. Genomic classification and prognosis in acute myeloid leukemia. N. Engl. J. Med. 374, 2209–2221 (2016). sourceExperimental — accuracy not yet measured
The Results section, “Driver-Mutation Landscape of AML” (page unavailable), identifies 76 AML driver genes or genomic regions, supporting the use of this paper for AML-related gene identification. It does not report a curated set of 622 genes, altered TADs, or the counts of 391 genes and more than 100 recurrent genes; those appear to be the citing authors’ own findings. (LLM, conf=0.78)
- Partly supportedcites [24] Sondka, Z. et al. The COSMIC Cancer Gene Census: describing genetic dysfunction across all human cancers. Nat. Rev. Cancer 18, 696–705 (2018). sourceExperimental — accuracy not yet measured
The Introduction describes the COSMIC Cancer Gene Census as a curated resource of cancer genes, supporting its use to identify such genes. But the Tier 2 section gives 719 genes in the August 2018 census, not the cited sentence’s combined set of 622 COSMIC cancer-related and AML-related genes. The 391 genes in altered TADs and their recurrence are presented as the citing authors’ own findings, not findings attributed to this source. (LLM, conf=0.84)
- Not checked yetcites [25] Metzeler, K. H. et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 128, 686–698 (2016). source
plain- Asserted: passes — The authors put it forward as true.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Peakachu reports a probability score associated with each loop which demarcates confidence of loop calling. The probability score is also positively associated with the loop intensity, making it convenient for differential loop analysis.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
What the sources say
- Partly supportedcites [27] Salameh, T. J. et al. A supervised learning framework for chromatin loop detection in genome-wide contact maps. Nat. Commun. 11, 3428 (2020). sourceExperimental — accuracy not yet measured
The Methods section, “Peakachu probability tuning” (page unavailable), says Peakachu assigns a probability to each pixel and uses it to filter loop calls; higher thresholds yield fewer, better-quality loops. The Results section, “Peakachu models are transferrable in different cell types” (page unavailable), uses changes in that score to identify cell-specific loops. Neither passage establishes that the probability score is positively associated with loop intensity. (LLM, conf=0.86)
plainstates an association- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Genes located in the A-to-B or B-to-A switching regions showed decreased or increased expression, respectively (Fig. 1e).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Subtype-specific compartmentalization
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“On average, there was 3.2% A-to-B compartment switch and 2.9% B-to-A switch comparing AML samples with HPSC controls (Fig. 1d).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Subtype-specific compartmentalization
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In the paper
“For example, the WT1 gene showed B-to-A switch and expression activation exclusively in samples with TET2 and/or FLT3-ITD mutations, accompanied by the gain of ATAC-seq and H3K27ac peaks (Extended Data Fig. 2a-b).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Subtype-specific compartmentalization
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“Correspondingly, we observed multiple gained chromatin loops appeared in these AML samples across the lost CTCF binding sites, including a loop linking WDR66 promoter with distal regions.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Altered DNA methylation and 3D genome
plainstates an associationn = 4- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, we observed in four AML samples (424, 018, 546, and 472) a lost binding of CTCF, the motif of which was hypermethylated in those samples (Bar plot in Extended Data Fig. 11g).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Altered DNA methylation and 3D genome
plainstates an associationn = 4- Asserted: passes — The authors put it forward as true.
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In the paper
“We observed variable methylation levels globally in AML samples (Extended Data Fig. 11a) and significantly higher methylation at CpG islands in AML compared with normal PBMC and HSPC (Fig. 6a), consistent with previous findings46.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Altered DNA methylation and 3D genome
What the sources say
- Not checked yetcites [46] Akalin, A. et al. Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia. PLoS Genet. 8, e1002781 (2012). source
plainstates an associationn = 18- Asserted: passes — The authors put it forward as true.
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In the paper
“As shown in Fig. 2e, 220 genes were significantly upregulated in AML and 88 genes were downregulated.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > AML-specific chromatin loops
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“Overall, we found 261 cancer-related genes whose promoters were located in the neo-loop anchors, 44 of which were recurrent across different samples.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Silencer hijacking
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, MYCN formed a subtype-specific interaction with a cluster of co-occurring enhancers ~650Kb downstream, and this loop was only observed in AML samples with TET2/FLT3-ITD, CEBPA or STAG2/KRAS/NRAS mutations (Fig. 2d).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > AML-specific chromatin loops
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“Across all samples, 42.4% of AML-specific loops were between gene promoter and enhancers (P-E), and 11.2% are between promoter and silencers (P-S) (Fig. 2g, Supplementary Table 2).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > AML-specific chromatin loops
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Overall, 5.7% of all the neo-loops in this study lead to silencer hijacking, while 17.2% of the neo-loops introduce enhancer-hijacking (Fig. 5e).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Silencer hijacking
plainstates a cause- Asserted: passes — The authors put it forward as true.
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“A representative example was shown in Extended Data Fig. 9c, where there was a fusion between chr7 and chr11 in AML 270, but not in HSPC. This neo-loop connected the CDK5 gene (located on chr7) to several enhancers on chr11. In contrast, there were no such inter-chromosomal Hi-C signals in HSPC.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Detecting enhancer hijacking in AML
plainstates an associationSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“We also identified the loss of CTCF binding sites in AML samples that were potentially due to hypermethylation (Extended Data Fig. 11d). There are in average 76 such sites in each AML samples.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Altered DNA methylation and 3D genome
hedgedstates a possible cause- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, the CBL gene was linked to enhancers on chr7 in sample 270, but in THP-1 cells, it was linked with enhancers on chr9 (Extended Data Fig. 9d);”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Detecting enhancer hijacking in AML
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“The AML-specific loops also showed subtype-specific patterns and contained many known AML proto-oncogenes (such as MYCN, WT1, ERG, MEIS1, and RUNX1) in the loop anchors (Fig. 2c).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > AML-specific chromatin loops
plainstates an association- Asserted: passes — The authors put it forward as true.
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In the paper
“P-S loops account for 9.2% of all loops, with an average size of 169 kb (Extended Data Fig. 6a and 6b).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > AML-specific chromatin loops
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“On average, each AML sample has 1.7 large deletions (>1 Mb), 2.1 inversions (>1 Mb), and 13.2 inter-chromosomal translocations (Supplementary Table 5).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Detecting enhancer hijacking in AML
plainn = 25- Asserted: passes — The authors put it forward as true.
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In the paper
“For example, the MYC gene (located on chr8) was looped with a cluster of enhancers on chr14 in sample 1360 due to t(8;14), but was looped with a different set of enhancers on chr11 in HL-60 cells due to t(8;11) (Fig. 4b).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Detecting enhancer hijacking in AML
plainstates a cause- Asserted: passes — The authors put it forward as true.
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In the paper
“The stable A compartments were slightly enriched for CpGi, while the stable B compartment regions were depleted of CpGi (Extended Data Fig. 13e).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
plainstates an association- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“865 out of the 905 (95.5%) TKD-induced A-to-B reversion regions overlapped with the A-to-B revision regions induced by 5-AZA treatment, and the overlap is 79% for the B-to-A reversion regions (Fig. 6f).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
plainstates an association- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We demonstrated that the HMA exposure partially restored the chromatin structure, including reverting switched compartment and dissociating AML-specific loops.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Discussion
boostedstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also showed the inter-chromosomal Hi-C map in the HSPC 213, where there is no visible inter-chromosomal interactions.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The treatment slowed down the cell proliferation (Extended Data Fig. 12a).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The diamond-shaped region between the two dashed lines resided the interactions across the lost CTCF sites.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The loops are absent in all three PBMC samples (only one is plotted) and less frequent in the four HSPC samples (only one is plotted).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Extended Data
plainn = 4- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AML sample 018 has the same loop but with less interacting signals and almost no H3K27me3 signals at the loop anchor.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Extended Data
plainSingle case- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the results showed that after 5-AZA treatment A/A and B/B interactions were decreased, while the interactions between A/B compartment were increased (Fig. 6i).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
plainstates a cause- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We noticed that the CpGi originally in A compartment (A-to-A and A-to-B) were hypomethylated, while CpGi originally in B compartment (B-to-B and B-to-A) were hypermethylated.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
plainstates an association- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“5-AZA treatment dramatically decreased DNA methylation levels for all four regions, with the biggest changes in open sea (Extended Data Fig. 13c), as well as on CTCF binding motifs (Extended Data Fig. 13d).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed increased interactions across the lost CTCF binding sites, suggesting that disruption of CTCF site might lead to loss of insulation and change the local chromatin interaction profile.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Altered DNA methylation and 3D genome
hedgedstates a possible causen = 4- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“SV calls from Delly and Speedseq were merged and only SVs detected by both methods were kept to reduce false positives.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Human blood samples were obtained with consent from AML patients or healthy donors under the Penn State Hershey IRB-approved protocol STUDY00005272.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The quantity and molecular size of the library was confirmed by Qubit HS DNA assay (ThermoFisher) and Tapestation 2200 system(Agilent).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In two separate replicates of experiments, lentiviruses of sgRNA plasmids were then transfected into 2 million of the treated Kasumi-1 cells with an MOI<0.3.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the detected SVs were compared against the DGV database (version 2016-05-15) to reduce germline SV calls.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This final set of point mutations was further used to confirm the clinical molecular diagnosis of our AML samples, and both results were used for optimizing the subtyping of the AML samples.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The qPCR was performed for RTTN RNA expression with the primer listed in Supplementary Table 11, using CRPSIR-processed Kasumi-1 cells without the deletion as the control.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All insertions have been verified by Sanger sequencing.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each cloning was verified by Sanger sequencing.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Myeloblasts accounted for more than 90% of purified PBMC for most samples”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Two biological replications were applied to each of CRISPR interference, CRISPR deletion, and reporter assay with similar results.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To control for cell number and transfection efficiency, firefly luciferase activity was normalized to renilla luciferase.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Read alignments were shifted +4bp on “+” strand and −5bp on “-” strand to account for Tn5 insertion before peak calling.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The Western Blots for yH2AX, Caspase-3, GAPDH, and β-actin under 5-AZA treatment were repeated for twice with similar results (Extended Data Fig. 12c-d).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Reads mapped to the same MboI restriction fragment are not informative to chromatin interactions and thus are removed for downstream analysis.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Each biological replicate contains three technical replicates.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The Western Blots for DNMT3A, DNMT3B, DNMT1, and GAPDH in the DNMT TKD experiment were repeated for three times with similar results (Fig. 7d).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To ensure specificity, we filter raw calls to retain stripes larger than 300kb (eight of 40Kb binds) to avoid calls that are less distinguishable from loop clusters or background noise.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“and minimal quality score of 20 was used to reduce false positive calls.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To minimize the number of germline calls, point mutations that overlap with dbSNP150 mutations were removed.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“measurements were taken in triplicates.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Peakachu detects loops as CTCF or H3K27ac loops depending on a pre-trained CTCF model or H3K27ac model.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
What the sources say
- Not checked yetcites [27] Salameh, T. J. et al. A supervised learning framework for chromatin loop detection in genome-wide contact maps. Nat. Commun. 11, 3428 (2020). source
plainstates a cause- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The library passed QC by the following parameters: skew ratio = 2.53 (criterial <10); perfect match = 91.5 (>70%); undetected guides = 0 (<0.5%); Coverage = ~5,500 per sgRNA (>100).”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Peaks in the ENCODE hg38 blacklist regions (http://mitra.stanford.edu/kundaje/akundaje/release/blacklists/hg38-human/hg38.blacklist.bed.gz) were filtered out.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cell proliferation was independently performed with three technical replicates every 24 hours.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In this work, loops were first detected using both models and only those detected by both models were reported to reduce the false positive loop calls.”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Informatics analysis
plainstates a cause- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
The paper relies on this without support.
AML is characterized by a global aberrant DNA methylation profile.
“AML is also characterized by a global aberrant DNA methylation profile.”
The paper relies on this without support.
Genome-wide enhancer hijacking in AML has not been studied.
“However, genome-wide enhancer hijacking in AML have not been studied.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“structural variations have the potential to rewire genes with ectopic regulatory elements”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > HMA/DNMT TKO reverses chromatin topology
“In a parallel effort, we treated the U937 cells with DNA hypomethylating agent 5-AZA, at a low but effective dosage (0.5μM for 12 days)”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Methods > Materials and Experiments
“U937 cells were cultured in either 0.5M 5-AZA or the same volume of DMSO for 12 days with alternate day drug media readministering.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Function of hijacked enhancers
“The CUT&Tag data showed specific depletion of H3K37ac signals at the two targeted loci (Extended Data Fig. 10c)”
§ Subtype-specific 3D genome alteration in acute myeloid leukemia > Extended Data
“c, H3K27ac at the sgRNA-targeted loci and the NSMCE3 gene promoter.”
Citations
Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816
Arber, D. A., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M. J., Le Beau, M. M., Bloomfield, C. D., Cazzola, M., & Vardiman, J. W. (2016) · Blood · doi:10.1182/blood-2016-03-643544 · Cited by 10,119
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Lieberman-Aiden, E., van Berkum, N. L., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B. R., Sabo, P. J., Dorschner, M. O., et al. (2009) · Science · doi:10.1126/science.1181369 · Cited by 8,898
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829
Self-citationDöhner, H., Estey, E. H., Grimwade, D. J., Amadori, S., Appelbaum, F. R., Büchner, T., Dombret, H., Ebert, B. L., Fenaux, P., Larson, R. A., et al. (2016) · Blood · doi:10.1182/blood-2016-08-733196 · Cited by 5,938
Self-citationBismark: a flexible aligner and methylation caller for Bisulfite-Seq applications
Krueger, F., & Andrews, S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr167 · Cited by 5,324
Research works printed but not linked: 1
- Spracklin, G. et al. Heterochromatin diversity modulates genome compartmentalization and loop extrusion barriers. Preprint at bioRxiv https://doi.org/10.1101/2021.08.05.455340 (2021). · DOI
Cited by
Sorted by citations
Cancer, metastasis, and the epigenome
Kiri, S., & Ryba, T. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02069-w · Cited by 228
“Acute myeloid leukemias, often karyotypically normal but with differentiation arrest, have been recently found to harbor characteristic alteration in TADs that enhance or silence genes required for leukemogenesis [194].”
BackgroundDileep, V., Boix, C. A., Mathys, H., Marco, A., Welch, G. M., Meharena, H. S., Loon, A., Jeloka, R., Peng, Z., Bennett, D. A., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.038 · Cited by 130
Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemia
Conn, V. M., Gabryelska, M., Toubia, J., Kirk, K., Gantley, L., Powell, J. A., Cildir, G., Marri, S., Liu, R., Stringer, B. W., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.002 · Cited by 75
Yu, L., Huang, K., Liao, Y., Wang, L., Sethi, G., & Ma, Z. (2024) · Cell Proliferation · doi:10.1111/cpr.13644 · Cited by 71
“95 Despite therapeutic drug administration being a core strategy for AML, its effectiveness is often hindered by low bioavailability, toxic side effects, and the need for intravenous administration.”
BackgroundLi, H., Han, Z., Sun, Y., Wang, F., Hu, P., Gao, Y., Bai, X., Peng, S., Ren, C., Xu, X., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50426-6 · Cited by 73
Self-citation
Metadata
- Authors
- Xu, J., Song, F., Lyu, H., Kobayashi, M., Zhang, B., Zhao, Z., Hou, Y., Wang, X., Luan, Y., Jia, B., Stasiak, L., Wong, J. H.-Y., Wang, Q., Jin, Q., Jin, Q., Fu, Y., Yang, H., Hardison, R. C., Dovat, S., Platanias, L. C., Diao, Y., Yang, Y., Yamada, T., Viny, A. D., Levine, R. L., Claxton, D., Broach, J. R., Zheng, H., & Yue, F.
- Affiliations
- Northwestern University (US)
- Penn State Cancer Institute (US)
- Pennsylvania State University (US)
- Duke University (US)
- Columbia University Irving Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Zheng, Hong
- Yue, Feng
- ORCID
- Xu, Jie
- Song, Fan
- Lyu, Huijue
- Kobayashi, Mikoto
- Zhang, Baozhen
- Hou, Ye
- Wang, Xiaotao
- Luan, Yu
- Wong, Josiah Hiu-yuen
- Wang, Qixuan
- Jin, Qi
- Jin, Qiushi
- Fu, Yihao
- Yang, Hongbo
- Hardison, Ross C.
- Dovat, Sinisa
- Platanias, Leonidas C.
- Diao, Yarui
- Yang, Yue
- Yamada, Tomoko
- Viny, Aaron D.
- Levine, Ross L.
- Claxton, David
- Broach, James. R.
- Zheng, Hong
- Yue, Feng
- Venue
- Nature
- Published
- 2022-10-26
- Volume
- 611
- Issue
- 7935
- Pages
- 387-398
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC10060167
- OpenAlex
- W4307659092
- Semantic Scholar
- 132618fe8c2b6c087d9eae40298458947550ac3b
- Cited by
- 208
- References
- 78
- Citations by year
- 2026: 38 · 2025: 61 · 2024: 68 · 2023: 40 · 2022: 1
- FWCI
- 31.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Damon Runyon Cancer Research Foundation (DRG 117-15, P30 CA008748)
- Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748, NIH P30CA008748)
- Edward P. Evans Foundation
- National Institutes of Health (CA008748, NIH P30 CA008748)
- National Institute on Drug Abuse (U01DA053691)
- National Human Genome Research Institute (R01HG011207, R01HG009906)
- National Cancer Institute (NIH P30 CA008748, R01CA213912, CA008748, U54CA143869, U01CA200060, R01CA216421, K08CA215317, P30CA008748, R35CA197594, P30CA014236)
- National Institute of General Medical Sciences (R35GM124820)
- National Institute of Diabetes and Digestive and Kidney Diseases (R24DK106766)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- acute myeloid leukemia, 3D genome organization, chromatin looping, A/B compartments, topologically associating domains, enhancer hijacking, CTCF binding, DNA methylation, DNMT1, DNMT3A, DNMT3B, hypomethylating agents, leukemia subtypes, CRISPR interference, CRISPR screen, cancer therapy targets
- MeSH terms
- CCCTC-Binding Factor, Chromatin, DNA (Cytosine-5-)-Methyltransferases, Enhancer Elements, Genetic, Humans, Promoter Regions, Genetic, Sulfites, Reproducibility of Results, Leukemia, Myeloid, Acute, Genome, Human, Gene Expression Regulation, Leukemic, Sequence Analysis, DNA Methylation, Gene Silencing, CRISPR-Cas Systems
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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Cited sources are checked with a language model’s help (gpt-6-sol).
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