Decoding transcriptional regulation via a human gene expression predictor.

Transcription factors (TFs) regulate cellular activities by controlling gene expression, but a predictive model describing how TFs quantitatively modulate human transcriptomes is lacking. We construct a universal human gene expression predictor named EXPLICIT-Human and utilize it to decode transcriptional regulation. Using the expression of 1613 TFs, the predictor reconstitutes highly accurate transcriptomes for samples derived from a wide range of tissues and conditions. The broad applicability of the predictor indicates that it recapitulates the quantitative relationships between TFs and target genes ubiquitous across tissues. Significant interacting TF-target gene pairs are extracted from the predictor and enable downstream inference of TF regulators for diverse pathways involved in development, immunity, metabolism, and stress response. A detailed analysis of the hematopoiesis process reveals an atlas of key TFs regulating the development of different hematopoietic cell lineages, and a portion of these TFs are conserved between humans and mice. The results demonstrate that our method is capable of delineating the TFs responsible for fate determination. Compared to other existing tools, EXPLICIT-Human shows a better performance in recovering the correct TF regulators.

An Arabidopsis expression predictor enables inference of transcriptional regulators for gene modules.

The regulation of gene expression by transcription factors (TFs) has been studied for a long time, but no model that can accurately predict transcriptome profiles based on TF activities currently exists. Here, we developed a computational approach, named EXPLICIT (Expression Prediction via Log-linear Combination of Transcription Factors), to construct a universal predictor for Arabidopsis to predict the expression of 29 182 non-TF genes using 1678 TFs. When applied to RNA-Seq samples from diverse tissues, EXPLICIT generated accurate predicted transcriptomes correlating well with actual expression, with an average correlation coefficient of 0.986. After recapitulating the quantitative relationships between TFs and their target genes, EXPLICIT enabled downstream inference of TF regulators for genes and gene modules functioning in diverse plant pathways, including those involved in suberin, flavonoid, glucosinolate metabolism, lateral root, xylem, secondary cell wall development or endoplasmic reticulum stress response. Our approach showed a better ability to recover the correct TF regulators when compared with existing plant tools, and provides an innovative way to study transcriptional regulation.

Iron deficiency triggered transcriptome changes in bread wheat.

A series of complex transport, storage and regulation mechanisms control iron metabolism and thereby maintain iron homeostasis in plants. Despite several studies on iron deficiency responses in different plant species, these mechanisms remain unclear in the allohexaploid wheat, which is the most widely cultivated commercial crop. We used RNA sequencing to reveal transcriptomic changes in the wheat flag leaves and roots, when subjected to iron limited conditions. We identified 5969 and 2591 differentially expressed genes (DEGs) in the flag leaves and roots, respectively. Genes involved in the synthesis of iron ligands i.e., nicotianamine (NA) and deoxymugineic acid (DMA) were significantly up-regulated during iron deficiency. In total, 337 and 635 genes encoding transporters exhibited altered expression in roots and flag leaves, respectively. Several genes related to MAJOR FACILITATOR SUPERFAMILY (MFS), ATP-BINDING CASSETTE (ABC) transporter superfamily, NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN (NRAMP) family and OLIGOPEPTIDE TRANSPORTER (OPT) family were regulated, indicating their important roles in combating iron deficiency stress. Among the regulatory factors, the genes encoding for transcription factors of BASIC HELIX-LOOP-HELIX (bHLH) family were highly up-regulated in both roots and the flag leaves. The jasmonate biosynthesis pathway was significantly altered but with notable expression differences between roots and flag leaves. Homoeologs expression and induction bias analysis revealed subgenome specific differential expression. Our findings provide an integrated overview on regulated molecular processes in response to iron deficiency stress in wheat. This information could potentially serve as a guideline for breeding iron deficiency stress tolerant crops as well as for designing appropriate wheat iron biofortification strategies.

[Application of sentinel lymph node biopsy by subareolar injection of blue dye in the treatment of breast carcinoma].

OBJECTIVE: To probe into the feasibility and accuracy of sentinel lymph node biopsy by subareolar injection of blue dye in the treatment of early-stage breast carcinoma. METHODS: Retrospective analysis of 25 cases of early-stage breast cancer who were carried out subareolar injection of blue dye method for sentinel lymph node biopsy. RESULTS: Of 25 cases, 24 were checked out sentinel lymph nodes. Check-out rate was 96.0%. Totally 62 sentinel lymph nodes were checked out, each patient had 2.5 nodes averagely. There were 5 cases with lymph node metastases in HE stain, and 7 cases with positive nodes in IHC stain. Sensitivity in this group was 87.5%; Accuracy 96.0%; False negative rate 12.5%; False positive rate 0. CONCLUSION: Application of sentinel lymph node biopsy by subareolar injection of blue dye in the treatment of early-stage breast carcinoma can also acquire high check-out rate and high accuracy.

[Colonoscopy in preoperative staging and treatment of colorectal cancer].

OBJECTIVES: To investigate the value of colonoscopy for the diagnosis and preoperative staging of colorectal cancer, and evaluate the significance of correct preoperative staging in guiding treatment. METHODS: 28 patients with colorectal cancer were examined by general colonoscopy, magnifying endoscopy and endoscopic ultrasonography before operation. Preoperative staging, and proper treatment protocols were made. RESULTS: Endoscopy revealed that 15 of the 28 patients had early colorectal cancer and 13 advanced colorectal cancer. The correct diagnosis rate for preoperative staging was 100%; the accuracy of penetrating depth was 89% (25/28). In the early cases, tumour invasion was confined to mucosal layer in 11 patients and submucosal layer in 4. Six patients with early cancers 6 cm from the anus were treated by endoscopic mucosa resection (EMR) or EMR combined with open surgery. No postoperative recurrence was found by endoscopy during the period of follow-up for 12 - 40 months. CONCLUSION: Correct preoperative staging for colorectal cancer is of important significance in guiding treatment, especially in early staging cases. In order to improve the quality of life for colorectal cancer patients, we should treat them with individualized operation based on curative resection.