Cancer metastasis is no longer viewed as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as successfully metastasizing cells assume new phenotypes while jettisoning older behaviors. The lack of a systemic understanding of this complex phenomenon has limited progress in developing treatments for metastatic disease. Because metastasis has traditionally been investigated in distinct physiological compartments, the integration of these complex and interlinked aspects remains a challenge for both systems-level experimental and computational modeling of metastasis. Here, we present some of the current perspectives on the complexity of cancer metastasis, the multiscale nature of its progression, and a systems-level view of the processes underlying the invasive spread of cancer cells. We also highlight the gaps in our current understanding of cancer metastasis as well as insights emerging from interdisciplinary systems biology approaches to understand this complex phenomenon.

Single-cell network analysis demonstrates species-conserved functional roles for pulmonary alveolar cell types.

This paper describes an area and power-efficient VLSI approach for implementing the discrete wavelet transform on streaming multielectrode neurophysiological data in real time. The VLSI implementation is based on the lifting scheme for wavelet computation using the symmlet4 basis with quantized coefficients and integer fixed-point data precision to minimize hardware demands. The proposed design is driven by the need to compress neural signals recorded with high-density microelectrode arrays implanted in the cortex prior to data telemetry. Our results indicate that signal integrity is not compromised by quantization down to 5-bit filter coefficient and 10-bit data precision at intermediate stages. Furthermore, results from analog simulation and modeling show that a hardware-minimized computational core executing filter steps sequentially is advantageous over the pipeline approach commonly used in DWT implementations. The design is compared to that of a B-spline approach that minimizes the number of multipliers at the expense of increasing the number of adders. The performance demonstrates that in vivo real-time DWT computation is feasible prior to data telemetry, permitting large savings in bandwidth requirements and communication costs given the severe limitations on size, energy consumption and power dissipation of an implantable device.

The yeast synthetic lethal genetic interaction network contains rich information about underlying pathways and protein complexes as well as new genetic interactions yet to be discovered. We have developed a graph diffusion kernel as a unified framework for inferring complex/pathway membership analogous to “friends” and genetic interactions analogous to “enemies” from the genetic interaction network. When applied to theSaccharomyces cerevisiaesynthetic lethal genetic interaction network, we can achieve a precision around 50% with 20% to 50% recall in the genome-wide prediction of new genetic interactions, supported by experimental validation. The kernels show significant improvement over previous best methods for predicting genetic interactions and protein co-complex membership from genetic interaction data.