Improved reliability of fingerprint authentication is achieved through a unique vascular fingerprint which increases accuracy and verifies liveness. (more...)

Researchers at University of California, Irvine, have responded to the worldwide growing demand for fast 3D microscopy in bioimaging, by creating iSPIM Box (Inclined Single Plane Imaging Microscope Box), an adapter for commercial body microscopes, which can be used to achieve high spatial and temporal resolution in live cell imaging with only simple sample preparation in common culture dishes. (more...)

Comparing independent high-throughput gene-expression experiments can generate hypotheses about which gene-expression programs are shared between particular biological processes. Current techniques to compare expression profiles typically involve choosing a fixed differential expression threshold to summarize results, potentially reducing sensitivity to small but concordant changes. We have developed a threshold-free algorithm called Rank-rank Hypergeometric Overlap (RRHO). This algorithm steps through two gene lists ranked by the degree of differential expression observed in two profiling experiments, successively measuring the statistical significance of the number of overlapping genes. The output is a graphical map that shows the strength, pattern and bounds of correlation between two expression profiles. The threshold-free and graphical aspects of RRHO complement other rank-based approaches such as Gene Set Enrichment Analysis (GSEA), for which RRHO is a 2D analog. Rank-rank overlap analysis is a sensitive, robust and web-accessible method for detecting and visualizing overlap trends between two complete, continuous gene-expression profiles.      (more...)

The invention is an apparatus and method for second harmonic optical coherence tomography of a sample comprising a laser coupled to an interferometer which has a reference arm and in a sample arm. A nonlinear crystal in the reference arm generates a second harmonic reference signal. The sample typically backscatters some second harmonic light into the sample arm. A broadband beam splitter optically coupled to the reference arm and sample arm combines the signals from the reference arm and sample arm into interference fringes and a dichroic beam splitter splits the interference fringes into a fundamental and second harmonic interference signal. A detector is optically coupled to the dichroic beam splitter detects interference fringes from which both an OCT and second harmonic OCT image can be constructed using a conventional data processor. (more...)

UC Researchers have developed a Field-Programmable-Gate-Array (FPGA) based hardware implementation that utilizes the FM-Index for exact pattern matching for string searching.  This method of FM-Index string matching has a higher effective throughput than brute force due to the higher number of character comparisons per cycle performed by the FM-Index.  Further, the speed of this method is in the order of two orders of magnitude greater than Bowtie software tools and ten to seventy times faster than the traditional method using FHAST.   (more...)

Optical trapping systems are commercially available through several companies. In these systems, the optical trap precision relies on the passive stability of the instrument itself, and therefore demands costly engineering solutions to limit environmental noise that can be coupled into the optomechanical components. Consequently, high-resolution measurements are not possible in common biological laboratory settings that typically lack appropriate vibration isolation and temperature stability.  Researchers at the University of California, Berkeley have developed an invention that addresses a critical problem currently limiting the performance of high-resolution optical traps: that the mechanical drift of optical components often results in physical drift in the location of an optical trap that obscures the displacement-of-interest. The motion of biological motor proteins that are specific to interacting with DNA often take steps along the double helix that is on the order of 0.3 nanometers in size. Accurate measurement of displacements on this scale requires that drift of the trap positions be limited to no more than a few angstroms. However, the current best-performing optical traps suffer from instrumental drift that is almost twice what can be tolerated. Owing to the critical role of these components in all optical trapping systems, and the previously undetectable levels of mechanical drift they undergo, we sought to measure the trap drift with angstrom-level precision using a new approach. This new approach has successfully measured for and corrected for the mechanical drift of these components and demonstrated that this novel invention is capable of consistently reducing the noise floor to levels that have not previously been accomplished.        (more...)

Evaluation License. (more...)

CE-Combinatorial Extension, Algorithms and Computer Programs for Comparing the 3-dimensional Structures of Protein Molecules.   Download Site License. (more...)

This invention enables new biological discoveries with respect to regulatory processes, in particular for realizing various strain designs or limiting bacterial adaptation to antibiotics. ChIP-seq and other traditionally laborious experimental techniques (gel shift assays) can be done to confirm specific predictions of a regulatory factor that may be affecting strain design rather than using blind approaches to discover interfering regulatory processes. The research this invention is based on can be found at this link. http://www.nature.com/ncomms/journal/v3/n7/full/ncomms1928.html (more...)

Genotoxic (DNA damage-inducing) chemicals often increase the risk of cancer. Genotoxicity testing is mandatory for approval of new drugs as an indicator of potential carcingenicity and is therefore genotoxicity is generally undesired. However, genotoxic activity can also in some cases be deliberately screened for to help identify DNA-targeting compounds, as leads for the development of antimicrobial, immunosuppressive, or antitumor agents. The most popular genotoxicity assay is the Ames’ test. This test uses Salmonella and E. coli as model organisms because of the exquisite conservation of DNA damage and repair mechanisms across kingdoms. The Ames’ test detects point mutations and frameshifts based on the reversion of inactivating mutations in the biosynthesis operon of a given amino acid. Because this assay detects mutations rather than more indirect effects of genotoxicity such as changes in gene expression, it has a high degree of specificity (77% compared to ~50% for other genotoxicity tests). However, the classic Ames’ test presents a number of technical limitations, notably the large amount of test sample required. The Ames’ test is not easily amenable to high throughput screening. Some high-throughput versions of the Ames’ test have been developed, and are based on fluctuation analysis in liquid culture. In this case the readout is binary (i.e. growth vs. no growth) in individual wells of a 96-well plate. UCSC researchers’ newly developed technology generates a quantitative signal that is proportional to the number of random mutations present in the culture. Thus, the information provided in a 96-well plate for the liquid Ames’ test could be obtained in one well, dramatically reducing the amount of test sample required. (more...)

Plant growth and development depends on the coordination of gene expression in a tissue-, temporal-, or signal-dependent manner. Often, the complex expression pattern observed for a given gene derives from regulation at both the transcriptional and post-transcriptional levels. This multi-layered approach to gene control is part of what makes plants robust, adaptable, and efficient as living photosynthetic systems. Complex gene regulation requires a multi-level approach. Current technology for transgene regulation in plants is based almost exclusively on transcriptional activation. For example, tissue-specific and stress-responsive promoters are extensively employed for inducible gene regulation, though many of these conditional promoters are species-specific. Alternative splicing of mRNA is an important mechanism of gene regulation in plants. The two possible consequences of alternative splicing of an mRNA are: (i) to change the protein coding sequence, by inserting or deleting sequences, or by shifting the reading frame, or (ii) to change the fate of the mRNA, by inserting or deleting sequences that target the RNA for degradation, localization, or other processes. This research has identified how to use RNA elements that regulate alternative splicing of mRNAs for inducible control of gene expression. (more...)

Bayesian networks are a popular class of graphical probabilistic models based on Bayes theorem. Bayesian networks represent a joint probability distribution over a set of variables. Once known, this joint distribution may be used to compute the probabilities of any configuration of the variables. Bayesian networks have been increasingly applied to various computation applications, such as computational biology and computer vision. The commonly used approach of modeling network behavior employs ordinary or partial differential equations (ODE or PDE), but this approach is limited to analyzing relatively small networks (10-20 nodes), as ODE or PDE approaches may consider only local effects in the network. There is need to overcome this limitation and provide a systematic way, based on biological networks, to evaluate the effects of inhibiting multiple drug targets on treating a disease. (more...)

It is often advantageous to ascertain the biological purpose of a gene product by "knocking out" that gene and observing the phenotypic consequence(s). This is most often accomplished in whole animal experiments that are costly and take long periods of time related to the gestation period of the animal system. Here we divulge a system where this goal can be accomplished in a short period of time in laboratory cultured animal cells. (more...)

Colon cancer is the third most common form of cancer in the United States. Therapy is usually invasive - surgery, followed by chemotherapy. Due to the lack of treatments that are effective for all cancer patients, there is a need to identify the patients that might benefit from specific anti-cancer drugs. Currently, dasatinib is approved to treat chronic myeloid leukemia (CML) and is in development to treat solid tumors, such as colon cancer. It would be useful to be able to predict the therapeutic effect of dasatinib and similar pharmaceuticals in individual colon cancer patients. (more...)

Sophisticated systems in nature, such as cells, tissues, and organs in the human body, are capable of responding intelligently to external stimuli. Such sophisticated responses involve the complex interplay of multiple variables comprising external stimuli and internal factors. This interplay can involve synergistic and antagonistic relationship amongst multiple variables.Therefore, it is very difficult to manipulate a system, such as a group of cells or tissue, to behave in a desirable or optimal way without understanding the following: the effect each variable has on the system, the different possible states of each variable and how those states affect the overall system, and the relationship amongst the variables. A solution to this approach is to test all the combinations of the different stimuli and the different states of each stimulus by parallel tests. The number of test required increase exponentially with the number of stimuli. For example, the effectiveness of a six-drug combination cocktail on a tissue or cell line, which if only ten different concentration per drug is used, requires 106 or 1 million parallel tests in order to identify the optimal concentration. (more...)

UCSD inventors have come up with an approach to patient selection and assessment of response to therapy that is very different from traditional pharmacogenomic approaches. This novel approach allows doctors to make various health prognosis tailored to individuals. It can also be used to estimate the life span, predisposition to diseases, and reaction to various chemotherapies in a variety of patient groupings. This invention would allow a company to profitably leverage the large sets of genome data soon to be available. (more...)

Historically, metabolic networks have been studied in a piecemeal fashion using biochemical, then genomic and proteomic approaches. The abundance and complexity of data dwarfed the ability to understand and use the information in an intelligent and integrated fashion. The development of systems-level, computational approaches have provided new tools for extracting useful information from the morass. (more...)

Family Pairwise Search (FPS) is a method for scoring a single biological sequence against a family of sequences. FPS compares pairs of sequences and then combines the pairwise scores into an overall score for the match of the single sequence to the family of sequences. FPS operates in two modes. In the single-sequence mode, FPS compares a single query sequence to a library of sequence families. The query consists of a single sequence, and the target library consists of families of sequences. The result is a family classification for the query sequence. In family-query mode, FPS compares a query set of related sequences to a database of single sequences. In this mode, FPS outputs a set of sequences from the database that are related to the query family. Further technical information on FPS may be found at the San Diego Supercomputer Center website address, fps.sdsc.edu. (more...)

Similarity search methods are important for data mining in many fields, such as biology, finance, and artificial intelligence. In molecular biology, for example, computer-assisted sequence comparison is widely recognized as an essential analytical tool. The quality of an alignment is usually characterized by an alignment score. Statistical significance (e.g., a p-or E- value) needs to be assigned to the alignment score in order to interpret the result. This statistics assessment is however a difficult and time-consuming task for the existing Smith-Waterman-type or HMM-based algorithms, whenever gaps are involved. A novel hybrid algorithm has recently been devised so that the alignments it generates obey universal statistics, without sacrificing the sensitivity and computational cost compared to the best of the existing methods. The alignment scores of the hybrid algorithm have been shown to satisfy the so-called Gumbel distribution, with the few Gumbel parameters readily computable, for a large class of scoring functions and for a wide range of sequence lengths and amino acid frequencies. These allow one to rapidly characterize the results of sequence comparison, without the need for extensive simulation for each scoring functions as it is currently done. The hybrid algorithm has been successfully tested on known classes of protein sequences. For more information, see: Y.-K. Yu and T. Hwa, Statistical Significance of Probabilistic Sequence Alignment and Related Local Hidden Markov Models, J. Comp. Biol., submitted for publication. (more...)

Researchers at UCSD have produced bioinformatics middleware for working with protein and nucleic acid macromolecular structure data stored in the new standard mmCIF format now being supported by the Protein Data Bank. The software will be very useful to researchers in basic and applied research in biology, biochemistry, pharmacology, medical research, molecular biology and protein chemistry. The toolkit contains software for parsing mmCIF files, loading the molecular structure data into a relational database, translating the data into XML formatted files, and running an OMG standard LSR/MMS CORBA server. The software is written entirely in Java. (more...)

This approach abandons the classical  "overlap - layout - consensus" approach in favor of a new graph approach that, for the first time, resolves the problem of repeats in fragment assembly. The graph approach, in contrast to the Celera assembler, does not mask repeats but uses them instead as a powerful fragment assembly tool. The software also works with 454 contigs. For general information about the EULER project see Pevzner, et al, PNAS, 98, 2001 and http://nbcr.sdsc.edu/euler/. Site License. (more...)

Knowledge of DNA gene sequences and other parts of the genome of organisms has become indispensable when studying biological processes, diagnostic research, and forensic research. Following the development of dye-based sequencing methods with automated analysis, DNA sequencing has become easier and faster by a magnitude of orders. The prominent rapid high-throughput DNA sequencing methods include Genome Sequencer using pyrosequencing by Roche/454, SOliD technology by Applied Biosystems, and the sequencing by synthesis technology employed by Ilumina/Solexa. Methods for real-time direct sequencing from single DNA molecules are also emerging. These include the SMART technology being developed by Pacific Biosciences and the FRET-based sequencing method by VisiGen Biotechnologies (a part of Life Technologies Incorporated). The use of fluorescent-labeled nucleotides in almost all current single molecule-sequencing methods with optical imaging presents numerous problems, including background fluorescence and the requirement for a polymerase capable of incorporating labeled nucleotides. (more...)

BACKGROUND:Several commonly used commercial ultra high-throughput (HTP) sequencing technologies share a common limitation: the instruments produce relatively short reads, typically shorter than 40 bases long. If longer reads are desirable, additional cycles can be run, but these additional cycles result in a dramatically increased error rate. Some competing HTP sequencing technologies provide longer average read lengths of approximately 200 bases, but severely limit the number of sequences that can be produced, namely 1/100 to even 1/1000 the number of sequences that the shorter read-length technologies can produce at equivalent overall cost. Thus, there is a need for new methods that would allow for longer read lengths for technologies able to produce in the tens or hundreds of millions of sequences. DESCRIPTION: UCSF scientists have developed a new method for significantly extending the read lengths obtained from ultra HTP sequencing technologies. This technique leverages the depth and redundancy of sequencing obtained from the ultra HTP sequencing technologies that currently produce tens or hundreds of millions of sequences to result in increased read lengths of up to approximately 130 bases. This method has been validated on both the Saccharomyces cerevisiae transcriptome and the more challenging Plasmodium falciparum transcriptome using an ultra high sequence number instrument. (more...)

Atomic Force Microscopy-based Platform for Investigating Single Cell Mechanics (more...)

BACKGROUND: Genetic engineering of bacteria has become a prevalent way of producing chemicals, providing a cost-effective, scalable, and environmentally safe manufacturing process. However, maximizing the final product titer remains a challenge, requiring the optimization of the bacteria’s metabolism and the identification of the optimal protein production rates. Currently, the production rates of these proteins are determined through trial and error, by random mutagenesis, or equivalent random selection methods. As such, the development costs are typically very high.   TECHNOLOGY:   UCSF researchers have developed a novel methodology that allows the user to select the production rate of a given protein from very low to very high rates (1 to 100000), thus eliminating the use of trial and error techniques during the optimization process and enabling extremely high protein expression levels. The method is accessible via interactive web-based software. (more...)