Macromolecular protein complexes carry out many of the essential functions of cells, and many genetic diseases arise from disrupting the functions of such complexes. Currently, there is great interest in defining the complete set of human protein complexes, but recent published maps lack comprehensive coverage. Here, through the synthesis of over 9,000 published mass spectrometry experiments, we present hu.MAP, the most comprehensive and accurate human protein complex map to date, containing > 4,600 total complexes, > 7,700 proteins, and > 56,000 unique interactions, including thousands of confident protein interactions not identified by the original publications. hu.MAP accurately recapitulates known complexes withheld from the learning procedure, which was optimized with the aid of a new quantitative metric (k‐cliques) for comparing sets of sets. The vast majority of complexes in our map are significantly enriched with literature annotations, and the map overall shows improved coverage of many disease‐associated proteins, as we describe in detail for ciliopathies. Using hu.MAP, we predicted and experimentally validated candidate ciliopathy disease genes in vivo in a model vertebrate, discovering CCDC138, WDR90, and KIAA1328 to be new cilia basal body/centriolar satellite proteins, and identifying ANKRD55 as a novel member of the intraflagellar transport machinery. By offering significant improvements to the accuracy and coverage of human protein complexes, hu.MAP (http://proteincomplexes.org) serves as a valuable resource for better understanding the core cellular functions of human proteins and helping to determine mechanistic foundations of human disease.

The three immunomarker-SVM-based prognostic characteristics are closely associated with overall survival among patients with stage IB NSCLC.

Growing evidence suggests that YAP/TAZ are mediators of the Hippo pathway and promote breast cancer. However, the roles of YAP/TAZ transcription factor partners TEADs in breast cancer remain unclear. Here we found that TEAD4 was expressed in breast cancer cell lines, especially in triple negative breast cancers (TNBC) cell lines. TEAD4 binds to KLF5. Knockdown of either TEAD4 or KLF5 in HCC1937 and HCC1806 cells induced the expression of CDK inhibitor p27. Depletion of either TEAD4 or KLF5 activated the p27 gene promoter and increased the p27 mRNA levels. Depletion of p27 partially prevents growth inhibition caused by TEAD4 and KLF5 knockdown. TEAD4 overexpression stimulated proliferation in vitro and tumor growth in mice, while stable knockdown of TEAD4 inhibited proliferation in vitro and tumor growth in mice. Thus TEAD4 and KLF5, in collaboration, promoted TNBC cell proliferation and tumor growth in part by inhibiting p27 gene transcription. TEAD4 is a potential target and biomarker for the development of novel therapeutics for breast cancer.

PurposePedicle screw fixation in the upper cervical spine is a difficult and high-risk procedure. The screw is difficult to place rapidly and accurately, and can lead to serious injury of spinal cord or vertebral artery. The aim of this study was to design an individualized 3D printing navigation template for pedicle screw fixation in the upper cervical spine.MethodsUsing CT thin slices data, we employed computer software to design the navigation template for pedicle screw fixation in the upper cervical spine (atlas and axis). The upper cervical spine models and navigation templates were produced by 3D printer with equal proportion, two sets for each case. In one set (Test group), pedicle screws fixation were guided by the navigation template; in the second set (Control group), the screws were fixed under fluoroscopy. According to the degree of pedicle cortex perforation and whether the screw needed to be refitted, the fixation effects were divided into 3 types: Type I, screw is fully located within the vertebral pedicle; Type II, degree of pedicle cortex perforation is <1 mm, but with good internal fixation stability and no need to renovate; Type III, degree of pedicle cortex perforation is >1 mm or with the poor internal fixation stability and in need of renovation. Type I and Type II were acceptable placements; Type III placements were unacceptable.ResultsA total of 19 upper cervical spine and 19 navigation templates were printed, and 37 pedicle screws were fixed in each group. Type I screw-placements in the test group totaled 32; Type II totaled 3; and Type III totaled 2; with an acceptable rate of 94.60%. Type I screw placements in the control group totaled 23; Type II totaled 3; and Type III totaled 11, with an acceptable rate of 70.27%. The acceptability rate in test group was higher than the rate in control group. The operation time and fluoroscopic frequency for each screw were decreased, compared with control group.ConclusionThe individualized 3D printing navigation template for pedicle screw fixation is easy and safe, with a high success rate in the upper cervical spine surgery.