Unified Signatures Research Articles

Desmoplastic stromal signatures predict patient outcomes in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related death. Hallmarks include desmoplasia with variable extracellular matrix (ECM) architecture and a complex microenvironment with spatially defined tumor, stromal, and immune populations. Nevertheless, the role of desmoplastic spatial organization in patient/tumor variability remains underexplored, which we elucidate using two technologies. First, we quantify ECM patterning in 437 patients, revealing architectures associated with disease-free and overall survival. Second, we spatially profile the cellular milieu of 78 specimens using codetection by indexing, identifying an axis of pro-inflammatory cell interactions predictive of poorer outcomes. We discover that clinical characteristics, including neoadjuvant chemotherapy status, tumor stage, and ECM architecture, correlate with differential stromal-immune organization, including fibroblast subtypes with distinct niches. Lastly, we define unified signatures that predict survival with areas under the receiver operating characteristic curve (AUCs) of 0.872-0.903, differentiating survivorship by 655days. Overall, our findings establish matrix ultrastructural and cellular organizations of fibrosis linked to poorer outcomes.

Genome-wide identification of potential biomarkers in multiple myeloma using meta-analysis of mRNA and miRNA expression data

Multiple myeloma (MM) is a plasma cell malignancy with diverse clinical phenotypes and molecular heterogeneity not completely understood. Differentially expressed genes (DEGs) and miRNAs (DEMs) in MM may influence disease pathogenesis, clinical presentation / drug sensitivities. But these signatures overlap meagrely plausibly due to complexity of myeloma genome, diversity in primary cells studied, molecular technologies/ analytical tools utilized. This warrants further investigations since DEGs/DEMs can impact clinical outcomes and guide personalized therapy. We have conducted genome-wide meta-analysis of DEGs/DEMs in MM versus Normal Plasma Cells (NPCs) and derived unified putative signatures for MM. 100 DEMs and 1,362 DEGs were found deranged between MM and NPCs. Signatures of 37 DEMs (‘Union 37’) and 154 DEGs (‘Union 154’) were deduced that shared 17 DEMs and 22 DEGs with published prognostic signatures, respectively. Two miRs (miR-16–2-3p, 30d-2-3p) correlated with survival outcomes. PPI analysis identified 5 topmost functionally connected hub genes (UBC, ITGA4, HSP90AB1, VCAM1, VCP). Transcription factor regulatory networks were determined for five seed DEGs with ≥ 4 biomarker applications (CDKN1A, CDKN2A, MMP9, IGF1, MKI67) and three topmost up/ down regulated DEMs (miR-23b, 195, let7b/ miR-20a, 155, 92a). Further studies are warranted to establish and translate prognostic potential of these signatures for MM.

Studying the Effect of Selection of the Sign and Ratio in the Formation of a Signature in a Program Identification Problem

Properties of using various assembler commands, as well as their combined application, have been investigated in order to prepare a final determination as to whether they belong to a known program. Conclusions on the effect of the ratio used in the creation of unified signatures on result of identifications are presented.

Improving Utilization of Hardware Signatures in Transactional Memory

The transactional memory (TM) paradigm promises to increase programmer productivity by making it easier to write correct parallel programs. In fulfilling this goal, a TM system should maximize its performance with limited hardware resources. Conflict detection is an essential element for maintaining correctness among concurrent transactions in a TM system. Hardware signatures have been proposed as an area-efficient method for detecting conflicts. However, signatures can degrade TM performance by falsely declaring conflicts. Hence, improving the accuracy of signatures within a given hardware budget is a crucial issue for TM to be adopted as a mainstream programming model. In this paper, we propose a simple and effective signature design, the unified signature. Instead of using separate read- and write-signatures, we implement a single signature to track all read- and write-accesses. By merging read- and write-signatures, a unified signature can effectively enlarge the signature coverage without additional overhead. Within the constraints of a given hardware budget, a TM system with a unified signature outperforms a baseline system with the same-sized traditional signatures by reducing the number of falsely detected conflicts. Even though the unified signature scheme incurs read-read dependencies, we show that these false dependencies do not negate the benefit of unified signatures and can effectively be filtered out. A TM system with a 2-Kbit unified signature with a helper signature scheme achieves speedups of 15 percent over baseline TM with 33 percent less area and 49 percent less power.