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1.
Am J Hum Genet ; 111(5): 841-862, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38593811

ABSTRACT

RNA sequencing (RNA-seq) has recently been used in translational research settings to facilitate diagnoses of Mendelian disorders. A significant obstacle for clinical laboratories in adopting RNA-seq is the low or absent expression of a significant number of disease-associated genes/transcripts in clinically accessible samples. As this is especially problematic in neurological diseases, we developed a clinical diagnostic approach that enhanced the detection and evaluation of tissue-specific genes/transcripts through fibroblast-to-neuron cell transdifferentiation. The approach is designed specifically to suit clinical implementation, emphasizing simplicity, cost effectiveness, turnaround time, and reproducibility. For clinical validation, we generated induced neurons (iNeurons) from 71 individuals with primary neurological phenotypes recruited to the Undiagnosed Diseases Network. The overall diagnostic yield was 25.4%. Over a quarter of the diagnostic findings benefited from transdifferentiation and could not be achieved by fibroblast RNA-seq alone. This iNeuron transcriptomic approach can be effectively integrated into diagnostic whole-transcriptome evaluation of individuals with genetic disorders.


Subject(s)
Cell Transdifferentiation , Fibroblasts , Neurons , Sequence Analysis, RNA , Humans , Cell Transdifferentiation/genetics , Fibroblasts/metabolism , Fibroblasts/cytology , Sequence Analysis, RNA/methods , Neurons/metabolism , Neurons/cytology , Transcriptome , Reproducibility of Results , Nervous System Diseases/genetics , Nervous System Diseases/diagnosis , RNA-Seq/methods , Female , Male
2.
Nature ; 467(7315): 570-3, 2010 Sep 30.
Article in English | MEDLINE | ID: mdl-20882012

ABSTRACT

Entanglement is one of the key resources required for quantum computation, so the experimental creation and measurement of entangled states is of crucial importance for various physical implementations of quantum computers. In superconducting devices, two-qubit entangled states have been demonstrated and used to show violations of Bell's inequality and to implement simple quantum algorithms. Unlike the two-qubit case, where all maximally entangled two-qubit states are equivalent up to local changes of basis, three qubits can be entangled in two fundamentally different ways. These are typified by the states |GHZ>= (|000+ |111>)/ sqrt [2] and |W>= (|001> + |010> + |100>)/ sqrt [3]. Here we demonstrate the operation of three coupled superconducting phase qubits and use them to create and measure |GHZ> and |W>states. The states are fully characterized using quantum state tomography and are shown to satisfy entanglement witnesses, confirming that they are indeed examples of three-qubit entanglement and are not separable into mixtures of two-qubit entanglement.

3.
Phys Rev Lett ; 105(17): 177001, 2010 Oct 22.
Article in English | MEDLINE | ID: mdl-21231072

ABSTRACT

We measure the lifetime (T1) and coherence (T2) of two-level defect states (TLSs) in the insulating barrier of a Josephson phase qubit and compare to the interaction strength between the two systems. We find for the average decay times a power-law dependence on the corresponding interaction strengths, whereas for the average coherence times we find an optimum at intermediate coupling strengths. We explain both the lifetime and the coherence results using the standard TLS model, including dipole radiation by phonons and anticorrelated dependence of the energy parameters on environmental fluctuations.

4.
Science ; 325(5941): 722-5, 2009 Aug 07.
Article in English | MEDLINE | ID: mdl-19661423

ABSTRACT

In quantum information processing, qudits (d-level systems) are an extension of qubits that could speed up certain computing tasks. We demonstrate the operation of a superconducting phase qudit with a number of levels d up to d = 5 and show how to manipulate and measure the qudit state, including simultaneous control of multiple transitions. We used the qudit to emulate the dynamics of single spins with principal quantum number s = 1/2, 1, and 3/2, allowing a measurement of Berry's phase and the even parity of integer spins (and odd parity of half-integer spins) under 2pi-rotation. This extension of the two-level qubit to a multilevel qudit holds promise for more-complex quantum computational architectures and for richer simulations of quantum mechanical systems.

5.
Phys Rev Lett ; 101(20): 200401, 2008 Nov 14.
Article in English | MEDLINE | ID: mdl-19113317

ABSTRACT

We demonstrate in a superconducting qubit the conditional recovery (uncollapsing) of a quantum state after a partial-collapse measurement. A weak measurement extracts information and results in a nonunitary transformation of the qubit state. However, by adding a rotation and a second partial measurement with the same strength, we erase the extracted information, canceling the effect of both measurements. The fidelity of the state recovery is measured using quantum process tomography and found to be above 70% for partial-collapse strength less than 0.6.

6.
Phys Rev Lett ; 100(24): 247001, 2008 Jun 20.
Article in English | MEDLINE | ID: mdl-18643615

ABSTRACT

We demonstrate new experimental procedures for measuring small errors in a superconducting quantum bit (qubit). By carefully separating out gate and measurement errors, we construct a complete error budget and demonstrate single qubit gate fidelities of 0.98, limited by energy relaxation. We also introduce a new metrology tool-- Ramsey interference error filter-that can measure the occupation probability of the state |2> which is outside the computational basis, down to 10{-4}, thereby confirming that our quantum system stays within the qubit manifold during single qubit logic operations.

7.
Phys Rev Lett ; 99(18): 187006, 2007 Nov 02.
Article in English | MEDLINE | ID: mdl-17995432

ABSTRACT

We present a new method to measure 1/f noise in Josephson quantum bits (qubits) that yields low-frequency spectra below 1 Hz. A comparison of the noise taken at positive and negative bias of a phase qubit shows the dominant noise source to be flux noise and not junction critical-current noise, with a magnitude similar to that measured previously in other systems. Theoretical calculations show that the level of flux noise is not compatible with the standard model of noise from two-level state defects in the surface oxides of the films.

8.
Phys Rev Lett ; 97(5): 050502, 2006 Aug 04.
Article in English | MEDLINE | ID: mdl-17026085

ABSTRACT

We introduce a new design concept for superconducting phase quantum bits (qubits) in which we explicitly separate the capacitive element from the Josephson tunnel junction for improved qubit performance. The number of two-level systems that couple to the qubit is thereby reduced by an order of magnitude and the measurement fidelity improves to 90%. This improved design enables the first demonstration of quantum state tomography with superconducting qubits using single-shot measurements.

9.
Science ; 313(5792): 1423-5, 2006 Sep 08.
Article in English | MEDLINE | ID: mdl-16960003

ABSTRACT

Demonstration of quantum entanglement, a key resource in quantum computation arising from a nonclassical correlation of states, requires complete measurement of all states in varying bases. By using simultaneous measurement and state tomography, we demonstrated entanglement between two solid-state qubits. Single qubit operations and capacitive coupling between two super-conducting phase qubits were used to generate a Bell-type state. Full two-qubit tomography yielded a density matrix showing an entangled state with fidelity up to 87%. Our results demonstrate a high degree of unitary control of the system, indicating that larger implementations are within reach.

10.
Science ; 312(5779): 1498-500, 2006 Jun 09.
Article in English | MEDLINE | ID: mdl-16763142

ABSTRACT

Measurement is one of the fundamental building blocks of quantum-information processing systems. Partial measurement, where full wavefunction collapse is not the only outcome, provides a detailed test of the measurement process. We introduce quantum-state tomography in a superconducting qubit that exhibits high-fidelity single-shot measurement. For the two probabilistic outcomes of partial measurement, we find either a full collapse or a coherent yet nonunitary evolution of the state. This latter behavior explicitly confirms modern quantum-measurement theory and may prove important for error-correction algorithms in quantum computation.

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