A method of analyzing an autoradiograph of plural resolved rows which are formed by resolving base-specific DNA fragments or base-specific RNA fragments labeled with a radioactive element in one-dimensional direction on a support medium, to determine the base sequence of nucleic acids by: (1) electrically displaying the autoradiograph as an image on a screen on the basis of digital signals corresponding to said autoradiograph; (2) displaying a read cursor on the screen; and (3) displaying a name of a base to which a band is assigned on the screen, which is determined by using the read cursor, together with the read cursor. A method of analyzing an autoradiograph which comprises recording and storing pattern information, cursor information and base sequence information, and a method which comprises verifying and/or correcting the determined sequence of bands are also disclosed.
A method and apparatus for the processing of DNA sequence image data in real time is implemented using a series of linked neural network processors. As raw image data is received from a sequencing machine, it is buffered and then separately transformed in real time in the processors to enhance the signals indicative of the unknown DNA sequence. A fourth processor receives the transformed data and determines and reports the sequence indicating events.
An apparatus includes an enclosed chamber in which a motor-driven cylinder is mounted for rotation about a horizontal axis. The lower half of the cylinder is disposed in a trough. A blot can be attached, analyte side outward, to the surface of the cylinder, and the cylinder is then rotated to carry the blot through a succession of treatment liquids, with which the trough is charged. Each liquid is discharged from the through before the next liquid is supplied. The liquid in the through can be maintained at any desired temperature above the ambient temperature. Water can be sprayed onto the blot to wash a liquid off and to flush the trough. The blot may be held in position on the cylinder by rollers which engage only the side edges of the blot.
An inexpensive manual reader for transcription of DNA sequence information from autoradiograms in computer data files is comprised of a gel code reader, electronic interface in software driven computer which provides full input and screening capability as well as storage and retrieval of DNA sequence data in predetermined DNA data base formats. The gel code reader comprises a linear optical magnifier and a thumb activated encoder. The electronic interface converts the data entered through the gel code reader into a plurality of computer compatible formats. The software driven computer then provides interactive voice synthesized editing and DNA data base storage.
The edit processing includes band deletion processing and band addition processing for correcting the DNA pattern image. Additionally, a concentration graph display indicative of a distribution of concentration of the DNA pattern is provided.
Normalization of experimental fragment patterns for nucleic acid polymers having putatively known sequences starts with obtaining at least one raw fragment pattern for the experimental sample. The raw fragment pattern represents the positions of a selected nucleic acid base within the polymer as a function of migration time or distance. This raw fragment pattern is conditioned using conventional baseline correction and noise reduction technique to yield a clean fragment pattern. The clean fragment pattern is then evaluated to determine one or more "normalization coefficients." These normalization coefficients reflect the displacement, stretching or shrinking, and rate of stretching or shrinking of the clean fragment, or segments thereof, which are necessary to obtain a suitably high degree of correlation between the clean fragment pattern and a standard fragment pattern which represents the positions of the selected nucleic acid base within a standard polymer actually having the known sequence as a function of migration time or distance. The normalization coefficients are then applied to the clean fragment pattern to produce a normalized fragment pattern which is used for base-calling in a conventional manner. This method may be implemented in an apparatus comprising a computer processor programmed to determine normalization coefficients for an experimental fragment pattern. This computer may be separate from the electrophoresis apparatus, or part of an integrated unit.