Nader Pourmand

University of California, Santa Cruz, Bme, Faculty Member

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Papers by Nader Pourmand

Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjögren’s syndrome and systemic lupus erythematosus

Annals of The Rheumatic Diseases, 1999

OBJECTIVETo investigate the occurrence of IgA autoantibodies to Ro 52 kDa, Ro 60 kDa and La antig... more OBJECTIVETo investigate the occurrence of IgA autoantibodies to Ro 52 kDa, Ro 60 kDa and La antigen in serum of patients with primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE).METHODSRecombinant Ro 52 kDa, Ro 60 kDa and La antigens were used to analyse autoantibodies in serum from 25 patients with pSS, 30 patients with SLE and 20 controls using

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A High-Density Magnetoresistive Biosensor Array with Drift-Compensation Mechanism

2007 IEEE International Solid-State Circuits Conference. Digest of Technical Papers, 2007

A DNA microarray of 1008 magnetoresistive sensors employing multidivided array structures for det... more A DNA microarray of 1008 magnetoresistive sensors employing multidivided array structures for detecting either tow concentration or large-scale gene information is integrated with a 0.25mum BiCMOS chip. The input-referred noise is below 55nV/radicHz. Ionic solution interferences and drifts during biological reaction are removed by applying an in-plane AC magnetic field with two DC field states. Parallel readout is realized by combining FDM with TDM.

You cannot tell a book by looking at the cover: Cryptic complexity in bacterial evolution

Biomicrofluidics, 2014

Do genetically closely related organisms under identical, but strong selection pressure converge ... more Do genetically closely related organisms under identical, but strong selection pressure converge to a common resistant genotype or will they diverge to different genomic solutions? This question gets at the heart of how rough is the fitness landscape in the local vicinity of two closely related strains under stress. We chose a Growth Advantage in Stationary Phase (GASP) E scherichia coli strain to address this question because the GASP strain has very similar fitness to the wild-type (WT) strain in the absence of metabolic stress but in the presence of metabolic stress continues to divide and does not enter into stationary phase. We find that under strong antibiotic selection pressure by the fluoroquinolone antibiotic ciprofloxacin in a complex ecology that the GASP strain rapidly evolves in under 20 h missense mutation in gyrA only 2 amino acids removed from the WT strain indicating a convergent solution, yet does not evolve the other 3 mutations of the WT strain. Further the GASP ...

PathogenMIPer: a tool for the design of molecular inversion probes to detect multiple pathogens

BMC bioinformatics, 2006

Here we describe PathogenMIPer, a software program for designing molecular inversion probe (MIP) ... more Here we describe PathogenMIPer, a software program for designing molecular inversion probe (MIP) oligonucleotides for use in pathogen identification and detection. The software designs unique and specific oligonucleotide probes targeting microbial or other genomes. The tool tailors all probe sequence components (including target-specific sequences, barcode sequences, universal primers and restriction sites) and combines these components into ready-to-order probes for use in a MIP assay. The system can harness the genetic variability available in an entire genome in designing specific probes for the detection of multiple co-infections in a single tube using a MIP assay. PathogenMIPer can accept sequence data in FASTA file format, and other parameter inputs from the user through a graphical user interface. It can design MIPs not only for pathogens, but for any genome for use in parallel genomic analyses. The software was validated experimentally by applying it to the detection of huma...

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CMOS Integrated DNA Microarray Based on GMR Sensors

2006 International Electron Devices Meeting, 2006

A high density GMR sensor array was integrated with a standard CMOS chip for DNA hybridization de... more A high density GMR sensor array was integrated with a standard CMOS chip for DNA hybridization detection. Absorption of magnetic nanoparticles by the hybridized DNA alters the sensor resistance, and generated electrical signals are directly measured with the on-die circuitry. The proposed biochip can be applied to other bio-reaction detection, e.g. protein assay, through different surface modifications

PathogenMip Assay: A Multiplex Pathogen Detection Assay

PLoS ONE, 2007

The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP ... more The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe. Citation: Akhras MS, Thiyagarajan S, Villablanca AC, Davis RW, Nyrén P, et al (2007) PathogenMip Assay: A Multiplex Pathogen Detection Assay. PLoS ONE 2(2): e223.

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$Research paper thumbnail of The molecular and pathway characterization of patients with metastatic castration resistant prostate cancer (mCRPC) refractory to therapy with abiraterone acetate or enzalutamide: Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT)$

The molecular and pathway characterization of patients with metastatic castration resistant prostate cancer (mCRPC) refractory to therapy with abiraterone acetate or enzalutamide: Preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT)

Hidden Complexity in Bacterial Evolution

HLA haplotyping from RNA-seq data using hierarchical read weighting

Correctly matching the HLA haplotypes of donor and recipient is essential to the success of allog... more Correctly matching the HLA haplotypes of donor and recipient is essential to the success of allogenic hematopoietic stem cell transplantation. Current HLA typing methods rely on targeted testing of recognized antigens or sequences. Despite advances in Next Generation Sequencing, general high throughput transcriptome sequencing is currently underutilized for HLA haplotyping due to the central difficulty in aligning sequences within this highly variable region. Here we present the method, HLAforest, that can accurately predict HLA haplotype by hierarchically weighting reads and using an iterative, greedy, top down pruning technique. HLAforest correctly predicts &amp;amp;amp;amp;gt;99% of allele group level (2 digit) haplotypes and 93% of peptide-level (4 digit) haplotypes of the most diverse HLA genes in simulations with read lengths and error rates modeling currently available sequencing technology. The method is very robust to sequencing error and can predict 99% of allele-group level haplotypes with substitution rates as high as 8.8%. When applied to data generated from a trio of cell lines, HLAforest corroborated PCR-based HLA haplotyping methods and accurately predicted 16/18 (89%) major class I genes for a daughter-father-mother trio at the peptide level. Major class II genes were predicted with 100% concordance between the daughter-father-mother trio. In fifty HapMap samples with paired end reads just 37 nucleotides long, HLAforest predicted 96.5% of allele group level HLA haplotypes correctly and 83% of peptide level haplotypes correctly. In sixteen RNAseq samples with limited coverage across HLA genes, HLAforest predicted 97.7% of allele group level haplotypes and 85% of peptide level haplotypes correctly.

Determination of hepatitis C virus genotype by Pyrosequencing

Journal of Virological Methods, 2003

A simple sequencing-based assay is described for genotyping of hepatitis C virus (HCV). RT-PCR wa... more A simple sequencing-based assay is described for genotyping of hepatitis C virus (HCV). RT-PCR was employed to amplify a 237-nucleotide-long fragment from the 5′ untranslated region (UTR) of the genome using one biotinylated and one normal primer. Subsequent to capture of the PCR products on streptavidin-coated beads, single-stranded DNA separation, and hybridization of sequencing primer, Pyrosequencing was performed. The genotype

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One-pot synthesis of monodisperse iron oxide nanoparticles for potential biomedical applications

Pure and Applied Chemistry, 2006

One-pot reaction of iron(III) acetylacetonate, Fe(acac)3, (or Fe(acac)3 and M(acac)2 where M = Mn... more One-pot reaction of iron(III) acetylacetonate, Fe(acac)3, (or Fe(acac)3 and M(acac)2 where M = Mn and Co), with 1,2-alkanediol, oleic acid, and oleylamine in high boiling organic solvent leads to monodisperse ferrite MFe2O4 nanoparticles. Depending on the concentration of the metal precursors, surfactant-to-metal precursor ratio and the solvent used in the reaction, the particle size from this one-pot reaction can be

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Copper sensing with a prion protein modified nanopipette

RSC Advances, 2012

Protein-metal interactions determine and regulate many biological functions. Nanopipettes functio... more

format_quoteThe PrP copper binding domain has a Kd of 0.12 nM, indicating strong binding affinity for Cu2+ ions, crucial for understanding prion peptide interactions.format_quote

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Molecular characterization of Neisseria gonorrhoeae identifies transmission and resistance of one ciprofloxacin-resistant strain: TRANSMISSION OF CIPROFLOXACIN-RESISTANT N. GONORRHOEAE

Apmis, 2007

A highly discriminative and objective genetic characterization of N. gonorrhoeae, which increases... more A highly discriminative and objective genetic characterization of N. gonorrhoeae, which increases our knowledge of strain populations in different geographic areas, is crucial for the development of improved control measures. In the present study, conventional phenotypic characterization and genetic characterization by means of pulsed-field gel electrophoresis (PFGE), sequencing of the entire porB gene, N. gonorrhoeae multiantigen sequence typing (NG-MAST), and pyrosequencing of a quinolone resistance determining region (QRDR) of the gyrA gene of Swedish ciprofloxacinresistant N. gonorrhoeae serovar IB-10 isolates (n=45) were performed. The genetic characterization identified one widely spread ciprofloxacin-resistant N. gonorrhoeae ST147 strain. In addition, isolates with slightly different genetic characteristics, which presumably reflect the ongoing evolution only, were also identified. All the isolates contained single nucleotide polymorphisms in QRDR of the gyrA gene that are highly correlated with ciprofloxacin resistance. Consequently, comprehensive characterization identified the first confirmed large domestic transmission, mainly among young heterosexuals, of one ciprofloxacin-resistant N. gonorrhoeae strain in Swedish society during 2002-2003. In conclusion, a precise, i.e. genetic, characterization for identification of individual strains is a very valuable support to the crucial active surveillance of the epidemiological characteristics and the antibiotic susceptibility of N. gonorrhoeae in the effective treatment of gonorrhoea.

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p16 INK4A immunohistochemical staining may be helpful in distinguishing branchial cleft cysts from cystic squamous cell carcinomas originating in the oropharynx

Cancer Cytopathology, 2009

BACKGROUND: We investigated p16 INK4A expression in branchial cleft cysts and its utility in dist... more BACKGROUND: We investigated p16 INK4A expression in branchial cleft cysts and its utility in distinguishing branchial cleft cysts from metastatic head and neck squamous cell carcinomas (SCCs) in fine-needle aspiration biopsies (FNABs). METHODS: A study set comprising 41 resections (15 SCC and 26 branchial cleft cysts) and a test set of 15 FNABs (11 SCC and 4 branchial cleft cysts) were analyzed with p16 INK4A immunohistochemistry and human papillomavirus (HPV) polymerase chain reaction (PCR)/pyrosequencing. Cases with discrepant p16 INK4A and PCR/pyrosequencing results were further evaluated with HPV in situ hybridization (ISH). SCCs were divided into keratinizing SCC and nonkeratinizing SCC groups and site of origin.

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A Label-free CMOS DNA Microarray based on Charge Sensing

2008 IEEE Instrumentation and Measurement Technology Conference, 2008

ABSTRACT

Functionalized nanopipettes: toward label-free, single cell biosensors

Bioanalytical Reviews, 2010

Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA an... more Nanopipette technology has been proven to be a label-free biosensor capable of identifying DNA and proteins. The nanopipette can include specific recognition elements for analyte discrimination based on size, shape, and charge density. The fully electrical read-out and the ease and low-cost fabrication are unique features that give this technology an enormous potential. Unlike other biosensing platforms, nanopipettes can be precisely manipulated with submicron accuracy and used to study single cell dynamics. This review is focused on creative applications of nanopipette technology for biosensing. We highlight the potential of this technology with a particular attention to integration of this biosensor with single cell manipulation platforms.

format_quoteNanopipettes can detect ionic current blockades by translocating DNA and differentiate between nanoparticle and oligonucleotide events, revealing specific signal patterns.format_quote

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Spin valve sensors for ultrasensitive detection of superparamagnetic nanoparticles for biological applications

Sensors and actuators. A, Physical, 2006

We present giant magnetoresistance (GMR) spin valve sensors designed for detection of superparama... more We present giant magnetoresistance (GMR) spin valve sensors designed for detection of superparamagnetic nanoparticles as potential biomolecular labels in magnetic biodetection technology. We discuss the sensor design and experimentally demonstrate that as few as approximately 23 monodisperse 16-nm superparamagnetic Fe(3)O(4) nanoparticles can be detected by submicron spin valve sensors at room temperature without resorting to lock-in detection. A patterned self-assembly method of nanoparticles, based on a polymer-mediated process and fine lithography, is developed for the detection. It is found that sensor signal increases linearly with the number of nanoparticles.

Simultaneous measurement of nonlinearity and electrochemical impedance for protein sensing using two-tone excitation

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2008

Impedance biosensors detect the binding of a target to an immobilized probe by quantifying change... more Impedance biosensors detect the binding of a target to an immobilized probe by quantifying changes in the impedance of the electrode-electrolyte interface. The interface's I-V relationship is inherently nonlinear, varying with DC bias, and target binding can alter the degree of nonlinearity. We propose and demonstrate a method to simultaneously measure the nonlinearity and conventional small-signal impedance using intermodulation products from a two-tone input. Intermodulation amplitudes accurately reflect the impedance's manually-measured voltage dependence. We demonstrate that changes in nonlinearity can discriminate protein binding. Our measurements suggest that target binding can alter nonlinearity via the voltage dependence of the ionic double layer.

Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing

by Nader Pourmand, Shahid Khan, and B. Emerson

Proceedings of the National Academy of Sciences, 2014

The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cel... more The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drugtolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy. single cell | paclitaxel | tumor heterogeniety | drug resistance | RNA-Seq

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Use of Whole Genome Sequencing to Determine the Microevolution of Mycobacterium tuberculosis during an Outbreak

PLoS ONE, 2013

Rationale: Current tools available to study the molecular epidemiology of tuberculosis do not pro... more Rationale: Current tools available to study the molecular epidemiology of tuberculosis do not provide information about the directionality and sequence of transmission for tuberculosis cases occurring over a short period of time, such as during an outbreak. Recently, whole genome sequencing has been used to study molecular epidemiology of Mycobacterium tuberculosis over short time periods.

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