Assessing reproducibility of high‐throughput experiments in the case of missing data

Singh, Roopali; Zhang, Feipeng; Li, Qunhua

doi:10.1002/sim.9334

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…It demonstrates the usefulness of segCCR for designing reliable and cost‐effective high‐throughput workflows. An extension for handling missing data due to underdetection in high‐throughput experiments (Singh et al., 2022) will be useful.…”

Section: Discussionmentioning

confidence: 99%

Segmented Correspondence Curve Regression for Quantifying Covariate Effects on the Reproducibility of High-Throughput Experiments

Zhang

2022

Biometrics

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High‐throughput biological experiments are essential tools for identifying biologically interesting candidates in large‐scale omics studies. The results of a high‐throughput biological experiment rely heavily on the operational factors chosen in its experimental and data‐analytic procedures. Understanding how these operational factors influence the reproducibility of the experimental outcome is critical for selecting the optimal parameter settings and designing reliable high‐throughput workflows. However, the influence of an operational factor may differ between strong and weak candidates in a high‐throughput experiment, complicating the selection of parameter settings. To address this issue, we propose a novel segmented regression model, called segmented correspondence curve regression, to assess the influence of operational factors on the reproducibility of high‐throughput experiments. Our model dissects the heterogeneous effects of operational factors on strong and weak candidates, providing a principled way to select operational parameters. Based on this framework, we also develop a sup‐likelihood ratio test for the existence of heterogeneity. Simulation studies show that our estimation and testing procedures yield well‐calibrated type I errors and are substantially more powerful in detecting and locating the differences in reproducibility across workflows than the existing method. Using this model, we investigated an important design question for ChIP‐seq experiments: How many reads should one sequence to obtain reliable results in a cost‐effective way? Our results reveal new insights into the impact of sequencing depth on the binding‐site identification reproducibility, helping biologists determine the most cost‐effective sequencing depth to achieve sufficient reproducibility for their study goals.

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Section: Discussionmentioning

confidence: 99%

Segmented Correspondence Curve Regression for Quantifying Covariate Effects on the Reproducibility of High-Throughput Experiments

Zhang

2022

Biometrics

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“…The filtered reads were then employed to identify CUT&Tag peaks using MACS2 (81). The overlapped peaks in the two biological replicates were identified by the Irreproducibility Discovery Rate (IDR) (82). Final peaks were annotated against the latest T. gondii reference genome in ToxoDB.…”

Section: Methodsmentioning

confidence: 99%

Cyclical transcription factor AP2XII-9 is a key activator for asexual division and apicoplast inheritance inToxoplasma gondiitachyzoite

Shi,

Li,

Xue

et al. 2024

Preprint

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Toxoplasma gondii is an intracellular parasitic protozoan that poses a significant risk to pregnant women and immunocompromised individuals. T. gondii tachyzoites duplicate rapidly in host cells during acute infection through endodyogeny. This highly regulated division process is accompanied by complex gene regulation networks. TgAP2XII-9 is a cyclical transcription factor, but its specific role in the parasite cell cycle is not fully understood. Here, we demonstrate that TgAP2XII-9 is identified as a nuclear transcription factor and is dominantly expressed during the S/M phase of the tachyzoite cell cycle. CUT&Tag results indicate that TgAP2XII-9 targets key genes for the moving junction machinery (RON2, 4, 8) and daughter cell inner membrane complex (IMC). TgAP2XII-9 deficiency resulted in a significant downregulation of rhoptry proteins and rhoptry neck proteins, leading to a severe defect in the invasion and egress efficiency of tachyzoites. Additionally, the loss of TgAP2XII-9 correlated with a substantial downregulation of multiple IMC and apicoplast proteins, leading to disorders of daughter bud formation and apicoplast inheritance, and further contributing to the inability of cell division and intracellular proliferation. Our study reveals that TgAP2XII-9 acts as a critical S/M-phase regulator that orchestrates the endodyogeny and apicoplast division in T. gondii tachyzoite. This study contributes to a broader understanding of the complexity of the parasite's cell cycle and its key regulators.

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“…The filtered reads were then employed to identify Cut-Tag peaks using MACS2 [48]. The overlapping peaks in two biological replicates were identified by the Irreproducibility Discovery Rate (IDR) [49]. The final peaks were annotated against the latest T. gondii data in ToxoDB.…”

Section: Cut-tag and Data Analysismentioning

confidence: 99%

AP2XII-1 and AP2XI-2 Suppress Schizogony Gene Expression in Toxoplasma gondii

Jiang,

Shi,

Xue

et al. 2024

IJMS

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Toxoplasma gondii is an intracellular parasite that is important in medicine and veterinary science and undergoes distinct developmental transitions in its intermediate and definitive hosts. The switch between stages of T. gondii is meticulously regulated by a variety of factors. Previous studies have explored the role of the microrchidia (MORC) protein complex as a transcriptional suppressor of sexual commitment. By utilizing immunoprecipitation and mass spectrometry, constituents of this protein complex have been identified, including MORC, Histone Deacetylase 3 (HDAC3), and several ApiAP2 transcription factors. Conditional knockout of MORC or inhibition of HDAC3 results in upregulation of a set of genes associated with schizogony and sexual stages in T. gondii tachyzoites. Here, our focus extends to two primary ApiAP2s (AP2XII-1 and AP2XI-2), demonstrating their significant impact on the fitness of asexual tachyzoites and their target genes. Notably, the targeted disruption of AP2XII-1 and AP2XI-2 resulted in a profound alteration in merozoite-specific genes targeted by the MORC–HDAC3 complex. Additionally, considerable overlap was observed in downstream gene profiles between AP2XII-1 and AP2XI-2, with AP2XII-1 specifically binding to a subset of ApiAP2 transcription factors, including AP2XI-2. These findings reveal an intricate cascade of ApiAP2 regulatory networks involved in T. gondii schizogony development, orchestrated by AP2XII-1 and AP2XI-2. This study provides valuable insights into the transcriptional regulation of T. gondii growth and development, shedding light on the intricate life cycle of this parasitic pathogen.

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Assessing reproducibility of high‐throughput experiments in the case of missing data

Cited by 5 publications

References 18 publications

Segmented Correspondence Curve Regression for Quantifying Covariate Effects on the Reproducibility of High-Throughput Experiments

Segmented Correspondence Curve Regression for Quantifying Covariate Effects on the Reproducibility of High-Throughput Experiments

Cyclical transcription factor AP2XII-9 is a key activator for asexual division and apicoplast inheritance inToxoplasma gondiitachyzoite

AP2XII-1 and AP2XI-2 Suppress Schizogony Gene Expression in Toxoplasma gondii

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