INVESTIGATING INVASION IN DUCTAL CARCINOMA IN SITU WITH TOPOGRAPHICAL SINGLE CELL GENOME SEQUENCING

Synchronous Ductal Carcinoma in situ (DCIS-IDC) is an early stage breast cancer invasion in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) regions, these studies were either confounded by bulk tissue or limited to a small set of genes or markers. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS), which combines laser-catapulting with single cell DNA sequencing to measure genomic copy number profiles from single tumor cells while preserving their spatial context. We applied TSCS to sequence 1,293 single cells from 10 synchronous DCIS patients. We also applied deep-exome sequencing to the in situ, invasive and normal tissues for the DCIS-IDC patients. Previous bulk tissue studies had produced several conflicting models of tumor evolution. Our data support a multiclonal invasion model, in which genome evolution occurs within the ducts and gives rise to multiple subclones that escape the ducts into the adjacent tissues to establish the invasive carcinomas. In summary, we have developed a novel method for single cell DNA sequencing, which preserves spatial context, and applied this method to understand clonal evolution during the transition between carcinoma in situ to invasive ductal carcinoma

Multiple degree of freedom optical pattern recognition

Three general optical approaches to multiple degree of freedom object pattern recognition (where no stable object rest position exists) are advanced. These techniques include: feature extraction, correlation, and artificial intelligence. The details of the various processors are advanced together with initial results

Waveform considerations in space-variant optical processors

The use of coded waveforms in space-variant optical signal processors using coordinate transformations is considered. It is shown that nonlinear transmitted coded signals must be used with such a processor and that this results in novel waveform design and system approaches for radar and communications

Iterative optical vector-matrix processors (survey of selected achievable operations)

An iterative optical vector-matrix multiplier with a microprocessor-controlled feedback loop capable of performing a wealth of diverse operations was described. A survey and description of many of its operations demonstrates the versatility and flexibility of this class of optical processor and its use in diverse applications. General operations described include: linear difference and differential equations, linear algebraic equations, matrix equations, matrix inversion, nonlinear matrix equations, deconvolution and eigenvalue and eigenvector computations. Engineering applications being addressed for these different operations and for the IOP are: adaptive phased-array radar, time-dependent system modeling, deconvolution and optimal control

Iterative color-multiplexed, electro-optical processor

A noncoherent optical vector-matrix multiplier using a linear LED source array and a linear P-I-N photodiode detector array has been combined with a 1-D adder in a feedback loop. The resultant iterative optical processor and its use in solving simultaneous linear equations are described. Operation on complex data is provided by a novel color-multiplexing system

Optical processing for landmark identification

A study of optical pattern recognition techniques, available components and airborne optical systems for use in landmark identification was conducted. A data base of imagery exhibiting multisensor, seasonal, snow and fog cover, exposure, and other differences was assembled. These were successfully processed in a scaling optical correlator using weighted matched spatial filter synthesis. Distinctive data classes were defined and a description of the data (with considerable input information and content information) emerged from this study. It has considerable merit with regard to the preprocessing needed and the image difference categories advanced. A optical pattern recognition airborne applications was developed, assembled and demontrated. It employed a laser diode light source and holographic optical elements in a new lensless matched spatial filter architecture with greatly reduced size and weight, as well as component positioning toleranced

A high-accuracy optical linear algebra processor for finite element applications

Optical linear processors are computationally efficient computers for solving matrix-matrix and matrix-vector oriented problems. Optical system errors limit their dynamic range to 30-40 dB, which limits their accuray to 9-12 bits. Large problems, such as the finite element problem in structural mechanics (with tens or hundreds of thousands of variables) which can exploit the speed of optical processors, require the 32 bit accuracy obtainable from digital machines. To obtain this required 32 bit accuracy with an optical processor, the data can be digitally encoded, thereby reducing the dynamic range requirements of the optical system (i.e., decreasing the effect of optical errors on the data) while providing increased accuracy. This report describes a new digitally encoded optical linear algebra processor architecture for solving finite element and banded matrix-vector problems. A linear static plate bending case study is described which quantities the processor requirements. Multiplication by digital convolution is explained, and the digitally encoded optical processor architecture is advanced

Novel parallel architectures and algorithms for linear algebra processors

Number representations, processing architectures and algorithms, optical linear algebra processor fabrication and test results, case study descriptions, and future system plans are covered