Discovering unknown human and mouse transcription factor binding sites and their characteristics from ChIP-seq data.

Transcription factor binding sites (TFBSs) are essential for gene regulation, but the number of known TFBSs remains limited. We aimed to discover and characterize unknown TFBSs by developing a computational pipeline for analyzing ChIP-seq (chromatin immunoprecipitation followed by sequencing) data. Applying it to the latest ENCODE ChIP-seq data for human and mouse, we found that using the irreproducible discovery rate as a quality-control criterion resulted in many experiments being unnecessarily discarded. By contrast, the number of motif occurrences in ChIP-seq peak regions provides a highly effective criterion, which is reliable even if supported by only one experimental replicate. In total, we obtained 2,058 motifs from 1,089 experiments for 354 human TFs and 163 motifs from 101 experiments for 34 mouse TFs. Among these motifs, 487 have not previously been reported. Mapping the canonical motifs to the human genome reveals a high TFBS density ±2 kb around transcription start sites (TSSs) with a peak at -50 bp. On average, a promoter contains 5.7 TFBSs. However, 70% of TFBSs are in introns (41%) and intergenic regions (29%), whereas only 12% are in promoters (-1 kb to +100 bp from TSSs). Notably, some TFs (e.g., CTCF, JUN, JUNB, and NFE2) have motifs enriched in intergenic regions, including enhancers. We inferred 142 cobinding TF pairs and 186 (including 115 completely) tethered binding TF pairs, indicating frequent interactions between TFs and a higher frequency of tethered binding than cobinding. This study provides a large number of previously undocumented motifs and insights into the biological and genomic features of TFBSs.

Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic.

Understanding the emergence of novel viruses requires an accurate and comprehensive annotation of their genomes. Overlapping genes (OLGs) are common in viruses and have been associated with pandemics but are still widely overlooked. We identify and characterize ORF3d, a novel OLG in SARS-CoV-2 that is also present in Guangxi pangolin-CoVs but not other closely related pangolin-CoVs or bat-CoVs. We then document evidence of ORF3d translation, characterize its protein sequence, and conduct an evolutionary analysis at three levels: between taxa (21 members of Severe acute respiratory syndrome-related coronavirus), between human hosts (3978 SARS-CoV-2 consensus sequences), and within human hosts (401 deeply sequenced SARS-CoV-2 samples). ORF3d has been independently identified and shown to elicit a strong antibody response in COVID-19 patients. However, it has been misclassified as the unrelated gene ORF3b, leading to confusion. Our results liken ORF3d to other accessory genes in emerging viruses and highlight the importance of OLGs.

Imaging active faulting in the western Taiwan Strait.

Large, destructive historical earthquakes off the coast of China's Fujian Province point to important tectonic activity in the western Taiwan Strait that, until recently, has received little attention. We present newly acquired reflection seismic data that is used to study the shallow crustal structure of the western Taiwan Strait. With these data we map the location of the Benhai fault for the first time, describe its upper crustal geometry and, in combination with seismicity and earthquake focal mechanisms, interpret its kinematics. These new data demonstrate that there is wide spread evidence of faulting that reaches the sea floor in the western Taiwan Strait, clearly indicating that the Benhai fault is active. Faults that cut up section from steep basin sidewalls to form flower structures or terraced sidewall fault zones, together with the fault and basin map pattern, are consistent with this fault zone being in the early developmental stages of a dextral strike-slip system. Earthquake focal mechanisms, although not definitive, support the model of an active dextral strike-slip fault system in the western Taiwan Strait.

Designing a tailored Web-based educational mammography program.

Breast cancer has become increasingly prevalent in Taiwanese women, especially in younger women. Unfortunately, early breast cancer detection may be hampered by Taiwanese women's beliefs about breast cancer, risk factors, and mammography. The Internet has become a powerful way to disseminate health information, but health education Web sites are frequently neither patient-centered nor theoretically based. We used the Transtheoretical Model as the theoretical basis for the design of a tailored Web-based educational program aimed at correcting Taiwanese women's misconceptions about breast cancer and mammography and increasing their intent to obtain routine mammography. In this article, we describe the Web-based educational intervention and the results of an initial preliminary evaluation study.