Faculty Opinions recommendation of Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription-related factors.

Author(s):  
Hans Lehrach
2012 ◽  
Vol 13 (9) ◽  
pp. R48 ◽  
Author(s):  
Kevin Y Yip ◽  
Chao Cheng ◽  
Nitin Bhardwaj ◽  
James B Brown ◽  
Jing Leng ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chathura J. Gunasekara ◽  
Eilis Hannon ◽  
Harry MacKay ◽  
Cristian Coarfa ◽  
Andrew McQuillin ◽  
...  

AbstractEpigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a “risk distance” to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearson r = 0.28, P = 1.28 × 10−12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants.


2021 ◽  
pp. 097215092110056
Author(s):  
Kanupriya Sethi ◽  
Baidyanath Biswas ◽  
Krishna Chandra Balodi

Adoption of an electronic marketplace (EM) business model for business-to-business (B2B) transactions has increased over the years. In part, this evolution and adoption of B2B EMs can be explained by the Internet-enabled disintermediation of the existing value chains of businesses, followed by cybermediation. This study aims to understand the platform architecture design and governance-related factors and strategic choices that influence the success of B2B EM start-ups. We draw from the literature on the ‘Temple Framework’ and the classification of B2B EMs by transaction content, structure, and governance to identify these critical factors. Given that the literature is primarily based in the context of developed economies, the factors and choices identified from the review are empirically validated using three case studies in the Indian B2B context. Thus, this exploratory study aims to help founder managers of emerging-economy B2B EMs by providing a checklist to avoid common pitfalls.


Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 183 ◽  
Author(s):  
Rizk Melissa ◽  
Mattar Lama ◽  
Kern Laurence ◽  
Berthoz Sylvie ◽  
Duclos Jeanne ◽  
...  

Abnormally high levels of physical activity have been documented throughout the literature in patients with eating disorders (ED), especially those diagnosed with anorexia nervosa (AN). Yet no clear definition, conceptualization, or treatment of the problematic use of physical activity (PPA) in ED patients exists. The aim of this review is to propose a new classification of PPA, report the prevalence, triggers, predictors, maintainers and other related factors of PPA in ED patients, in addition to proposing a comprehensive model of the development of PPA in AN. A total of 47 articles, retrieved from Medline and Web of Science, met the inclusion criteria and were included in the analysis. As a result, the new approach of PPA was divided into two groups (group 1 and group 2) according to the dimension (quantitative vs qualitative approach) of physical activity that was evaluated. The prevalence of PPA in ED was reported in 20 out of 47 studies, the comparison of PPA between ED versus controls in 21 articles, and the links between PPA and psychological factors in ED in 26 articles, including depression (16/26), anxiety (13/26), obsessive–compulsiveness (9/26), self-esteem (4/26), addictiveness (1/26), regulation and verbal expression of emotions (1/26) and anhedonia (1/26). The links between PPA and ED symptomatology, PPA and weight, body mass index (BMI) and body composition in ED, PPA and age, onset, illness duration and lifetime activity status in ED, PPA and ED treatment outcome were reported in 18, 15, 7, 5 articles, respectively. All of the factors have been systematically clustered into group 1 and group 2. Results focused more on AN rather than BN due to the limited studies on the latter. Additionally, a model for the development of PPA in AN patients was proposed, encompassing five periods evolving into three clinical stages. Thus, two very opposite components of PPA in AN were suggested: voluntarily PPA increased in AN was viewed as a conscious strategy to maximize weight loss, while involuntarily PPA increased proportionally with weight-loss, indicating that exercise might be under the control of a subconscious biological drive and involuntary cognition.


2018 ◽  
Author(s):  
Mehran Karimzadeh ◽  
Michael M. Hoffman

AbstractMotivationIdentifying transcription factor binding sites is the first step in pinpointing non-coding mutations that disrupt the regulatory function of transcription factors and promote disease. ChIP-seq is the most common method for identifying binding sites, but performing it on patient samples is hampered by the amount of available biological material and the cost of the experiment. Existing methods for computational prediction of regulatory elements primarily predict binding in genomic regions with sequence similarity to known transcription factor sequence preferences. This has limited efficacy since most binding sites do not resemble known transcription factor sequence motifs, and many transcription factors are not even sequence-specific.ResultsWe developed Virtual ChIP-seq, which predicts binding of individual transcription factors in new cell types using an artificial neural network that integrates ChIP-seq results from other cell types and chromatin accessibility data in the new cell type. Virtual ChIP-seq also uses learned associations between gene expression and transcription factor binding at specific genomic regions. This approach outperforms methods that predict TF binding solely based on sequence preference, pre-dicting binding for 36 transcription factors (Matthews correlation coefficient > 0.3).AvailabilityThe datasets we used for training and validation are available at https://virchip.hoffmanlab.org. We have deposited in Zenodo the current version of our software (http://doi.org/10.5281/zenodo.1066928), datasets (http://doi.org/10.5281/zenodo.823297), predictions for 36 transcription factors on Roadmap Epigenomics cell types (http://doi.org/10.5281/zenodo.1455759), and predictions in Cistrome as well as ENCODE-DREAM in vivo TF Binding Site Prediction Challenge (http://doi.org/10.5281/zenodo.1209308).


2021 ◽  
Author(s):  
Tom van Schaik ◽  
Ning Qing Liu ◽  
Stefano G. Manzo ◽  
Daan Peric-Hupkes ◽  
Elzo de Wit ◽  
...  

Lamina associated domains (LADs) are large genomic regions that are positioned at the nuclear lamina (NL). It has remained largely unclear what drives the positioning and demarcation of LADs. Because the insulator protein CTCF is enriched at LAD borders, it was postulated that CTCF binding could position a subset of LAD boundaries, possibly through its function in stalling cohesin and hence preventing cohesin to invade into the LAD. To test this, we mapped genome - NL interactions in mouse embryonic stem cells after rapid depletion of CTCF and other perturbations of cohesin dynamics. CTCF and cohesin contribute to a sharp transition in NL interactions at LAD borders, whilst LADs are maintained after depletion of these proteins, also at borders marked by CTCF. CTCF and cohesin may thus reinforce LAD borders, but do not position these. CTCF binding sites within LADs are locally detached from the NL and enriched for accessible DNA and active histone modifications. Remarkably, even though NL positioning is strongly correlated with genome inactivity, this DNA remains accessible after the local detachment is lost following CTCF depletion. At a chromosomal scale, cohesin depletion and cohesin stabilization (depletion of the unloading factor WAPL) quantitatively affect NL interactions, indicative of perturbed chromosomal positioning in the nucleus. Finally, while H3K27me3 is locally enriched at CTCF-marked LAD borders, we find no evidence for an interplay between CTCF and H3K27me3 on NL interactions. Combined, these findings illustrate that CTCF and cohesin do not shape LAD patterns. Rather, these proteins mediate fine-tuning of NL interactions.


2014 ◽  
Vol 15 (6) ◽  
pp. R88 ◽  
Author(s):  
Vincenza Colonna ◽  
Qasim Ayub ◽  
Yuan Chen ◽  
Luca Pagani ◽  
Pierre Luisi ◽  
...  

2020 ◽  
Vol 21 (24) ◽  
pp. 9421
Author(s):  
Lidia Skuza ◽  
Ewa Filip ◽  
Izabela Szućko ◽  
Jan Bocianowski

Secale is a small but very diverse genus from the tribe Triticeae (family Poaceae), which includes annual, perennial, self-pollinating and open-pollinating, cultivated, weedy and wild species of various phenotypes. Despite its high economic importance, classification of this genus, comprising 3–8 species, is inconsistent. This has resulted in significantly reduced progress in the breeding of rye which could be enriched with functional traits derived from wild rye species. Our previous research has suggested the utility of non-coding sequences of chloroplast and mitochondrial DNA in studies on closely related species of the genus Secale. Here we applied the SPInDel (Species Identification by Insertions/Deletions) approach, which targets hypervariable genomic regions containing multiple insertions/deletions (indels) and exhibiting extensive length variability. We analysed a total of 140 and 210 non-coding sequences from cpDNA and mtDNA, respectively. The resulting data highlight regions which may represent useful molecular markers with respect to closely related species of the genus Secale, however, we found the chloroplast genome to be more informative. These molecular markers include non-coding regions of chloroplast DNA: atpB-rbcL and trnT-trnL and non-coding regions of mitochondrial DNA: nad1B-nad1C and rrn5/rrn18. Our results demonstrate the utility of the SPInDel concept for the characterisation of Secale species.


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