Detection algorithm for the validation of human cell lines.

Cell lines are an important tool in understanding all aspects of cancer growth, development, metastasis and tumor cell death. There has been a dramatic increase in the number of cell lines and diversity of the cancers they represent; however, misidentification and cross-contamination of cell lines can lead to erroneous conclusions. One method that has gained favor for authenticating cell lines is the use of short tandem repeats (STR) to generate a unique DNA profile. The challenge in validating cell lines is the requirement to compare the large number of existing STR profiles against cell lines of interest, particularly when considering that the profiles of many cell lines have drifted over time and original samples are not available. We report here methods that analyze the variations and the proportional changes extracted from tetra-nucleotide repeat regions in the STR analysis. This technique allows a paired match between a target cell line and a reference database of cell lines to find cell lines that match within a user designated percentage cut-off quality matrix. Our method accounts for DNA instability and can suggest whether the target cell lines are misidentified or unstable.

A concentric morphology model for the detection of masses in mammography.

We propose a technique for the automated detection of malignant masses in screening mammography. The technique is based on the presence of concentric layers surrounding a focal area with suspicious morphological characteristics and low relative incidence in the breast region. Mammographic locations with high concentration of concentric layers with progressively lower average intensity are considered suspicious deviations from normal parenchyma. The multiple concentric layers (MCLs) technique was trained and tested using the craniocaudal views of 270 mammographic cases with biopsy proven malignant masses from the digital database of screening mammography. One-half of the available cases were used for optimizing the parameters of the detection algorithm. The remaining cases were used for testing. During testing, malignant masses were detected with 92%, 88%, and 81% sensitivity at 5.4, 2.4, and 0.6 false positive marks per image. Testing on 82 normal screening mammograms showed a false positive rate of 5.0, 1.7, and 0.2 marks per image at the previously reported operating points. Furthermore, additional evaluation on 135 benign cases produced a significantly lower detection rate for benign masses (61.6%, 58.3%, and 43.7% at 5.1, 2.8, and 1.2 false positives per image, respectively). Overall, MCL is a promising computer-assisted detection strategy for screening mammograms to identify malignant masses while maintaining the detection rate of benign masses considerably lower.

Systematic identification of combinatorial drivers and targets in cancer cell lines.

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

Significance of MPEG-7 textural features for improved mass detection in mammography.

The purpose of the study is to investigate the significance of MPEG-7 textural features for improving the detection of masses in screening mammograms. The detection scheme was originally based on morphological directional neighborhood features extracted from mammographic regions of interest (ROIs). Receiver Operating Characteristics (ROC) was performed to evaluate the performance of each set of features independently and merged into a back-propagation artificial neural network (BPANN) using the leave-one-out sampling scheme (LOOSS). The study was based on a database of 668 mammographic ROIs (340 depicting cancer regions and 328 depicting normal parenchyma). Overall, the ROC area index of the BPANN using the directional morphological features was Az=0.85+/-0.01. The MPEG-7 edge histogram descriptor-based BPNN showed an ROC area index of Az=0.71+/-0.01 while homogeneous textural descriptors using 30 and 120 channels helped the BPNN achieve similar ROC area indexes of Az=0.882+/-0.02 and Az=0.877+/-0.01 respectively. After merging the MPEG-7 homogeneous textural features with the directional neighborhood features the performance of the BPANN increased providing an ROC area index of Az=0.91+/-0.01. MPEG-7 homogeneous textural descriptor significantly improved the morphology-based detection scheme.

Morphological concentric layer analysis for automated detection of suspicious masses in screening mammograms.

Computer assisted detection systems (CAD) in mammography incorporate two critical stages: (i) prescreening to localize suspicious regions and (ii) detailed analysis of the regions for false positive reduction. In this work, we present a new technique for automatic detection of suspicious masses for prescreening mammograms. The hypothesis of the proposed technique is that malignant masses manifestate as superimposed concentric layers. Morphological characterization of these layers can form the foundation of an automated scheme for detection of suspicious masses. The study was based on fifty nine screening mammograms from the digital database of screening mammography (DDSM). Overall, the proposed scheme performs at 85.7% sensitivity with an average of 0.53 false positives per image. The scheme targets malignant masses and, thus it can provide a second opinion to radiologists without sending benign masses to unnecessary biopsy.